Objective Hepatocellular carcinoma(HCC)is sensitive to ferroptosis,a new form of programmed cell death that occurs in most tumor types.However,the mechanism through which ferroptosis modulates HCC remains unclear.This...Objective Hepatocellular carcinoma(HCC)is sensitive to ferroptosis,a new form of programmed cell death that occurs in most tumor types.However,the mechanism through which ferroptosis modulates HCC remains unclear.This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy.Methods Using clinicopathological parameters and bioinformatic techniques,we comprehensively examined the expression of FANCD2 macroscopically and microcosmically.We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death.Results FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration.As an independent risk factor for HCC,a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade.Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism.Conclusion To the best of our knowledge,this is the first study to comprehensively elucidate the oncogenic role of FANCD2.FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC;hence,it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.展开更多
Background:Although the prognostic nutritional index(PNI)may predict surgical outcomes in certain cancers,the impact of PNI on surgical prognosis in patients undergoing pylorus-preserving pancreati-coduodenectomy(PPPD...Background:Although the prognostic nutritional index(PNI)may predict surgical outcomes in certain cancers,the impact of PNI on surgical prognosis in patients undergoing pylorus-preserving pancreati-coduodenectomy(PPPD)is unclear.This study aimed to investigate the impact of preoperative PNI on mortality rate and cancer recurrence rate in patients who underwent PPPD.Methods:A total of 718 patients who were diagnosed with periampullary or pancreatic cancer and un-derwent PPPD between January 2012 and December 2016 were analyzed.Patients were categorized into two groups using the optimal cut-offvalue for PNI,determined by calculating the receiver operating characteristic(ROC)curve and the Youden index.We performed propensity score matching(PSM)anal-ysis to compare the mortality rate and cancer recurrence rate between the two groups.In addition,Cox regression analyses were performed to examine the association of PNI with mortality rate and cancer recurrence rate.Results:Using the 1-year mortality as an endpoint,the area under the ROC curve for PNI was 0.620(opti-mal cut-offvalue:41.7).We observed significant differences in 1-year(P=0.001),5-year(P=0.002),and overall(P=0.001)mortality;1-year(P=0.013),5-year(P=0.032),and overall(P=0.017)cancer re-currence between groups after PSM.High PNI was significantly associated with reduced 1-year[adjusted hazard ratio(HR)=0.44,95%confidence interval(CI):0.26-0.74,P=0.020],5-year(HR=0.66,95%CI:0.52-0.84,P<0.001),and overall(HR=0.71,95%CI:0.57-0.88,P=0.002)mortality;1-year(HR=0.70,95%CI:0.52-0.93,P=0.016),5-year(HR=0.78,95%CI:0.62-0.97,P=0.027)and overall(HR=0.78,95%CI:0.63-0.97,P=0.024)cancer recurrence.Conclusions:Preoperative PNI may serve as an independent factor for short-and long-term surgical prog-nosis in cancer patients undergoing PPPD.展开更多
Background:Lung cancer is the leading cause of cancer-related mortality,and while low-dose computed tomography screening may reduce mortality,emerging prognostic models show superior discriminative efficacy compared t...Background:Lung cancer is the leading cause of cancer-related mortality,and while low-dose computed tomography screening may reduce mortality,emerging prognostic models show superior discriminative efficacy compared to age-and smoking history-based screening.However,further research is needed to assess their reliability in predicting lung cancer risk in high-risk patients.Methods:This study evaluated the predictive performance and quality of existing lung cancer prognostic models through a systematic review and meta-analysis.A comprehensive search was conducted in PubMed,Cochrane,Web of Science,CNKI,and Wanfang for articles published between January 1,2000,and February 13,2025,identifying population-basedmodels incorporating all available modeling data.Results:Among 72 analyzed studies,models were developed from Asian(28 studies,including 23 Chinese cohorts)and European/American(48 studies)populations,with only 6 focusing on nonsmokers.Twenty-one models included genetic markers,15 used clinical factors,and 40 integrated epidemiological predictors.Although 37 models underwent external validation,only 4 demonstrated minimal bias and clinical applicability.A meta-analysis of 11 repeatedly validated models revealed calibration and discrimination,though some lacked calibration data.Conclusions:Few lung cancer prognostic models exist for nonsmokers.Most models exhibit poor predictive performance in external validations,with significant bias and limited application scope.Widespread external validation,standardized model development,and reporting techniques are needed to accurately identify high-risk individuals and ensure applicability across diverse populations.展开更多
BACKGROUND Among all solid tumors,pancreatic ductal adenocarcinoma(PDAC)is charac-terized by markedly poor survival outcomes,reflecting its high lethality,primarily as a result of late-stage diagnosis and limited trea...BACKGROUND Among all solid tumors,pancreatic ductal adenocarcinoma(PDAC)is charac-terized by markedly poor survival outcomes,reflecting its high lethality,primarily as a result of late-stage diagnosis and limited treatment options.Pancreatic adenocarcinoma upregulated factor(PAUF)displays elevated expression in PDAC compared to non-neoplastic pancreatic samples and is involved in promoting tumor development.However,its exact diagnostic and prognostic significance remains unclear.This study aimed to assess the clinical relevance of PAUF expression in PDAC.We hypothesized that higher PAUF expression is associated with more aggressive clinicopathological features and poorer patient outcomes.AIM To investigate the expression of PAUF in PDAC and its value as a diagnostic and prognostic biomarker.METHODS PAUF expression levels were assessed using immunohistochemistry in tumor tissues from 93 patients with PDAC.Staining intensity and the proportion of tumor cells showing PAUF positivity were assessed to categorize patients into low and high PAUF expression groups.Associations between PAUF expression and clinicopathological characteristics or survival outcomes were analyzed.Public datasets(The Cancer Genome Atlas,Genotype-Tissue Expression,and Clinical Proteomic Tumor Analysis Consortium)were employed to validate differences in PAUF expression in PDAC at mRNA and protein levels.RESULTS PAUF expression was observed in 82.8%of samples,primarily localized within the cytoplasm of tumor cells.High PAUF expression showed a significant correlation with metastasis to lymph nodes(78.4%,P=0.0019),indicating a strong association with advanced disease.Public datasets confirmed elevated PAUF levels at both transcript and protein levels in PDAC relative to normal tissue.Kaplan-Meier estimates indicated that higher PAUF levels were linked with shorter overall survival(18.4 months vs 32.7 months,P=0.032).Multivariate Cox regression confirmed high PAUF expression as a prognostically significant variable contributing to poor clinical outcomes[hazard ratio(HR)=2.05;P=0.009].Poor tumor differentiation(HR=2.47;P=0.004)and lack of adjuvant therapy(HR=0.39;P=0.001)were also independently associated with unfavorable outcomes.CONCLUSION PAUF is a promising biomarker for tumor progression and prognosis in PDAC,with potential clinical utility in early diagnosis and the development of targeted therapies.展开更多
BACKGROUND Lymph node status is a critical prognostic factor in gastric cancer(GC),but stage migration may occur in pathological lymph nodes(pN)staging.To address this,alternative staging systems such as the positive ...BACKGROUND Lymph node status is a critical prognostic factor in gastric cancer(GC),but stage migration may occur in pathological lymph nodes(pN)staging.To address this,alternative staging systems such as the positive lymph node ratio(LNR)and log odds of positive lymph nodes(LODDS)were introduced.AIM To assess the prognostic accuracy and stratification efficacy of three nodal staging systems in GC.METHODS A systematic review identified 12 studies,from which hazard ratios(HRs)for overall survival(OS)were summarized.Sensitivity analyses,subgroup analyses,publication bias assessments,and quality evaluations were conducted.To enhance comparability,data from studies with identical cutoff values for pN,LNR,and LODDS were pooled.Homogeneous stratification was then applied to generate Kaplan-Meier(KM)survival curves,assessing the stratification efficacy of three staging systems.RESULTS The HRs and 95%confidence intervals for pN,LNR,and LODDS were 2.16(1.72-2.73),2.05(1.65-2.55),and 3.15(2.15-4.37),respectively,confirming all three as independent prognostic risk factors for OS.Comparative analysis of HRs demonstrated that LODDS had superior prognostic predictive power over LNR and pN.KM curves for pN(N0,N1,N2,N3a,N3b),LNR(0.1/0.2/0.5),and LODDS(-1.5/-1.0/-0.5/0)revealed significant differences(P<0.001)among all prognostic stratifications.Mean differences and standard deviations in 60-month relative survival were 27.93%±0.29%,41.70%±0.30%,and 26.60%±0.28%for pN,LNR,and LODDS,respectively.CONCLUSION All three staging systems are independent prognostic factors for OS.LODDS demonstrated the highest specificity,making it especially useful for predicting outcomes,while pN was the most effective in homogeneous stratification,offering better patient differentiation.These findings highlight the complementary roles of LODDS and pN in enhancing prognostic accuracy and stratification.展开更多
Background:Small ubiquitin-like modifier(SUMO)-specific proteases(SENPs)cleave the isopeptidic bond between SUMO1/2/3 and protein substrates,thus regulating the structure,activity,and lifetime of a variety of proteins...Background:Small ubiquitin-like modifier(SUMO)-specific proteases(SENPs)cleave the isopeptidic bond between SUMO1/2/3 and protein substrates,thus regulating the structure,activity,and lifetime of a variety of proteins.Recently,accumulating evidence has suggested that SENPs play a role in the initiation and progression of human cancers.Nevertheless,the potential role of the SENP family of proteins in liver cancer has yet to be fully elucidated.Methods:This study conducted a comprehensive bioinformatics analysis of the SENP family in liver cancer,including differential expression profiling,survival analysis,mutation and copy number variations(CNVs)assessment,immune infiltration and drug sensitivity correlation,functional enrichment analyses using data from The Cancer Genome Atlas(TCGA),Clinical Proteomic Tumor Analysis Consortium(CPTAC),LinkedOmics,and other public databases.Furthermore,we performed in vitro experiments using Huh-7 and Hep-3B cell lines to investigate the functional roles of SENP1 and SENP3 in hepatocellular carcinoma cell proliferation,colony formation,and migration.Results:Our results indicated that SENP1,3,and 7 were significantly overexpressed in liver hepatocellular carcinoma(LIHC).Elevated expressions of SENP1,3,and 7 are positively correlated with poor overall survival(OS)in LIHC patients.In addition,SENP1,3,and 7 expressions are related to immune infiltration and drug sensitivity.SENP1,3,and 7 co-expressed genes were enriched in mitochondrial function,ribosomal translation,and cell cycle control.Conclusion:SENP1,3,and 7 are prognostic biomarkers and potential therapeutic targets for LIHC.Knockdown of SENP1 and SENP3 inhibited the proliferation,clonogenicity,and migration of hepatocellular carcinoma cells.展开更多
BACKGROUND Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6),a member of the ENTPD family,has been implicated in certain cancers,yet a comprehensive analysis across multiple cancer types remains lacking.AIM To ...BACKGROUND Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6),a member of the ENTPD family,has been implicated in certain cancers,yet a comprehensive analysis across multiple cancer types remains lacking.AIM To systematically evaluate ENTPD6’s expression,prognostic significance,and functions across multiple cancer types.METHODS In this study,we performed a pan-cancer analysis to investigate the correlation between ENTPD6 expression and various factors,including prognosis,genetic alterations,epigenetic modification,immune infiltration,immunotherapy responses,functional enrichment,and drug sensitivity.A tissue microarray of gastrointestinal tumors was used to validate differential ENTPD6 protein expression.RESULTS Pan-cancer analysis revealed that ENTPD6 expression was significantly elevated in many cancers.Immunohistochemistry staining analysis revealed that ENTPD6 expression was significantly higher in esophageal carcinoma,stomach adenocarcinoma,colon adenocarcinoma,rectal adenocarcinoma,and pancreatic adenocarcinoma compared to normal tissues.Furthermore,ENTPD6 expression was strongly associated with immune-infiltrating cells,particularly clusters of differentiation 8+T cells and natural killer cells,and correlated with immune-related genomic features including tumor mutational burden and microsatellite instability.Pathway analysis indicated that ENTPD6 expression was primarily linked to purine and pyrimidine metabolism pathways.Drug sensitivity analysis revealed that high ENTPD6 expression was sensitive to RDEA119,selumetinib,and PD-0325901.CONCLUSION This pan-cancer study elucidates the pivotal role of ENTPD6 in tumor progression and establishes its potential as a therapeutic target for immunotherapeutic approaches in specific malignancies.展开更多
BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further stu...BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence(P=0.030).The ROC curve indicated that Treg+Ki-67+age(≥65 years)combined could predict irAEs well(area under the curve=0.753,95%confidence interval:0.623-0.848,P=0.001).Results of the Kaplan-Meier survival curve showed that progressionfree survival(PFS)was longer in the irAEs group than in the non-irAEs group(P=0.001).Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS(P=0.006).CONCLUSION The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy.irAEs can affect the patients’PFS and result in longer PFS.Treg+Ki-67+age(≥65 years old)combined can better predict the occurrence of adverse reactions.展开更多
Background: Studies of gastrointestinal (GIT) cancers have shown that circZFR could be involved in the development and progression of various GIT cancers. However, small sample sizes limit the clinical significance of...Background: Studies of gastrointestinal (GIT) cancers have shown that circZFR could be involved in the development and progression of various GIT cancers. However, small sample sizes limit the clinical significance of these studies. Here, a meta-analysis was conducted to ascertain the actual involvement of circZFR in the development and prognosis of GIT cancers. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched up to December 31, 2023. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to evaluate the association between circZFR expression and overall survival (OS). Publication bias was measured using the funnel plot and Egger’s test. Results: 10 studies having 659 participants were enrolled for meta-analysis. High circZFR expression was associated with poor OS (HR = 1.4, 95% CI: 1.20, 1.70). High circZFR expression also predicted larger tumor size (OR = 4.38, 95% CI 2.65, 7.25), advanced clinical stage (OR = 5.33, 95% CI 3.10, 9.16), and tendency for distant metastasis (OR = 2.89, 95% CI: 1.62, 5.11), but was not related to age, gender, and histological grade. Conclusions: In summary, high circZFR expression was associated with poor OS, larger tumor size, advanced stage cancer and tendency for distant metastasis. These findings suggested that circZFR could be a prognostic marker for GIT cancers.展开更多
Background:Dihydrolipoamide S-acetyltransferase(DLAT)is a subunit of the pyruvate dehydrogenase complex(PDC),a rate-limiting enzyme complex,that can participate in either glycolysis or the tricarboxylic acid cycle(TCA...Background:Dihydrolipoamide S-acetyltransferase(DLAT)is a subunit of the pyruvate dehydrogenase complex(PDC),a rate-limiting enzyme complex,that can participate in either glycolysis or the tricarboxylic acid cycle(TCA).However,the pathogenesis is not fully understood.We aimed to perform a more systematic and comprehensive analysis of DLAT in the occurrence and progression of tumors,and to investigate its function in patients’prognosis and immunotherapy.Methods:The differential expression,diagnosis,prognosis,genetic and epigenetic alterations,tumor microenvironment,stemness,immune infiltration cells,function enrichment,single-cell analysis,and drug response across cancers were conducted based on multiple computational tools.Additionally,we validated its carcinogenic effect and possible mechanism in glioma cells.Results:We exhibited that DLAT expression was increased in most tumors,especially in glioma,and affected the survival of tumor patients.DLAT was related to RNA modification genes,DNA methylation,immune infiltration,and immune infiltration cells,including CD4+T cells,CD8+T cells,Tregs,and cancer-associatedfibroblasts.Single-cell analysis displayed that DLAT might regulate cancer by mediating angiogenesis,inflammation,and stemness.Enrichment analysis revealed that DLAT might take part in the cell cycle pathway.Increased expression of DLAT leads tumor cells to be more resistant to many kinds of compounds,including PI3Kβinhibitors,PKC inhibitors,HSP90 inhibitors,and MEK inhibitors.In addition,glioma cells with DLAT silence inhibited proliferation,migration,and invasion ability,and promoted cell apoptosis.Conclusion:We conducted a comprehensive analysis of DLAT in the occurrence and progression of tumors,and its possible functions and mechanisms.DLAT is a potential diagnostic,prognostic,and immunotherapeutic biomarker for cancer patients.展开更多
Background:The cyclin-dependent kinase inhibitor 2a(CDKN2A)gene,identified as the multiple tumor suppressor gene,functions as a regulatory gene implicated in cancer pathogenesis.Its significance lies in its pivotal in...Background:The cyclin-dependent kinase inhibitor 2a(CDKN2A)gene,identified as the multiple tumor suppressor gene,functions as a regulatory gene implicated in cancer pathogenesis.Its significance lies in its pivotal involvement in the genesis of various tumors;notwithstanding,the precise connection between CDKN2A and c olon adenocarcinoma(COAD)remains undisclosed.Methods:The objective of this research was to assess the predictive importance of CDKN2A in COAD by analyzing data from The Cancer Genome Atlas database.Logistic regression,signed rank test,Wilcoxon test,and Kruskal-Wallis test were used to examine CDKN2A expression levels and clinicopathological features.Univariate and multivariate Cox r egression analyses and Kaplan-Meier analysis found prognostic variables.Additionally,gene set enrichment analysis identified key CDKN2A expression pathways.The study additionally examined CDKN2A expression with tumor immune infiltration using The Cancer Genome Atlas data and single sample gene set enrichment analysis.Results:The results of this investigation indicated a substantial connection between higher CDKN2A expression and negative outcomes in terms of overall survival and disease-related survival among COAD patients.Gene set enrichment analysis indicated a tight link between CDKN2A and both the cell cycle and hedgehog signaling pathways.Subsequent evaluation employing single sample gene set enrichment analysis demonstrated a positive link between CDKN2A expression with infiltration by iDCs,whereas a negative correlation was detected with infiltration by helper T cells.Conclusion:In conclusion,the present study gives strong data supporting the predictive value of CDKN2A and its possible usefulness as a biomarker for COAD.Additionally,our results show a reasonable link between CDKN2A expression and immune influx in COAD,putting light on the role of CDKN2A in the control of the tumor microenvironment.Nevertheless,additional studies are needed to confirm the underlying mechanisms of these relationships and to discover the therapeutic possibilities of targeting CDKN2A in the treatment of COAD.展开更多
BACKGROUND In recent studies,accumulating evidence has revealed a strong association between the inflammatory response and the prognosis of many tumors.There is a certain correlation of neutrophil-to-lymphocyte ratio(...BACKGROUND In recent studies,accumulating evidence has revealed a strong association between the inflammatory response and the prognosis of many tumors.There is a certain correlation of neutrophil-to-lymphocyte ratio(NLR)with the prognosis in gastric cancer(GC)patients undergoing neoadjuvant chemotherapy(NAC).However,the existing research results have remained controversial.AIM To explore the relationship between NLR ratio and prognosis of GC patients receiving NAC.METHODS A thorough systematic search was performed in databases such as PubMed,Embase,Web of Science,and Cochrane Library,the search is available until February 29,2024,and studies exploring the interaction of NLR with clinical outcomes were collected.Relevant studies meeting pre-defined inclusion and exclusion criteria were carefully chosen.The outcomes included progression-free survival(PFS),relapse-free survival,disease-free survival(DFS),and overall survival(OS).The hazard ratio(HR)and its corresponding 95%confidence interval(CI)were utilized for estimation.RESULTS Our analysis encompassed 852 patients and incorporated data from 12 cohort studies.The comprehensive analysis revealed a significant association of high NLR with reduced OS(HR=1.76;95%CI:1.22-2.54,P=0.003),relapsefree survival(HR=3.73;95%CI:1.74-7.96,P=0.0007),and PFS(HR=2.32;95%CI:1.42-3.81,P=0.0008)in patients.However,this correlation in disease-free survival was not significant.NLR demonstrated its crucial role in effectively predicting the OS of GC patients undergoing NAC at different detection times,ages,regions,and NLR thresholds.CONCLUSION In GC patients receiving NAC,an elevated NLR is strongly associated with reduced OS and PFS.NLR has become an effective biomarker for patient prognosis evaluation,providing valuable insights for the treatment strategies of NAC in GC patients.展开更多
BACKGROUND Traditional methods cannot clearly visualize esophageal cancer(EC)tumor contours and metastases,which limits the clinical application of da Vinci robotassisted surgery.AIM To investigate the efficacy of the...BACKGROUND Traditional methods cannot clearly visualize esophageal cancer(EC)tumor contours and metastases,which limits the clinical application of da Vinci robotassisted surgery.AIM To investigate the efficacy of the da Vinci robot in combination with nanocarbon lymph node tracers in radical surgery of EC.METHODS In total,104 patients with early-stage EC who were admitted to Liuzhou worker's Hospital from January 2020 to June 2023 were enrolled.The patients were assigned to an observation group(n=52),which underwent da Vinci robot-assisted minimally invasive esophagectomy(RAMIE)with the intraoperative use of nanocarbon tracers,and a control group(n=52),which underwent traditional surgery treatment.The operation time,intraoperative blood loss,postoperative drainage tube indwelling time,hospital stay,number of lymph nodes dissected,incidence of complications,and long-term curative effects were comparatively analyzed.The postoperative stress response C-reactive protein(CRP),cortisol,epinephrine(E)and inflammatory response interleukin(IL)-6,IL-8,IL-10,and tumor necrosis factor-alpha(TNF-α)were evaluated.RESULTS Compared with the control group,the observation group had significantly lower postoperative CRP,cortisol,and E levels(P<0.05)with a milder inflammatory response,as indicated by lower IL-6,IL-10,and TNF-αlevels(P<0.05).Patients who underwent RAMIE had less intraoperative blood loss and shorter operation times and hospital stays than those who underwent traditional surgery.The average number of dissected lymph nodes,time of lymph node dissection,and mean smallest lymph node diameter were all significantly lower in the observation group(P<0.05).The rate of postoperative complications was 5.77%in the observation group,significantly lower than the 15.38%observed in the control group.Furthermore,the lymphatic metastasis rate,reoperation rate,and 12-and 24-month cumulative mortality in the observation group were 1.92%,0%,0%,and 0%,respectively,all of which were significantly lower than those in the control group(P<0.05).CONCLUSION The treatment of EC using the da Vinci robot combined with nanocarbon lymph node tracers can achieve good surgical outcomes and demonstrates promising clinical applications.展开更多
BACKGROUND Rebleeding after recovery from esophagogastric variceal bleeding(EGVB)is a severe complication that is associated with high rates of both incidence and mortality.Despite its clinical importance,recognized p...BACKGROUND Rebleeding after recovery from esophagogastric variceal bleeding(EGVB)is a severe complication that is associated with high rates of both incidence and mortality.Despite its clinical importance,recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are lacking.AIM To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal rebleeding.METHODS This study included 477 EGVB patients across 2 cohorts:The derivation cohort(n=322)and the validation cohort(n=155).The primary outcome was rebleeding events within 1 year.The least absolute shrinkage and selection operator was applied for predictor selection,and multivariate Cox regression analysis was used to construct the prognostic model.Internal validation was performed with bootstrap resampling.We assessed the discrimination,calibration and accuracy of the model,and performed patient risk stratification.RESULTS Six predictors,including albumin and aspartate aminotransferase concentrations,white blood cell count,and the presence of ascites,portal vein thrombosis,and bleeding signs,were selected for the rebleeding event prediction following endoscopic treatment(REPET)model.In predicting rebleeding within 1 year,the REPET model ex-hibited a concordance index of 0.775 and a Brier score of 0.143 in the derivation cohort,alongside 0.862 and 0.127 in the validation cohort.Furthermore,the REPET model revealed a significant difference in rebleeding rates(P<0.01)between low-risk patients and intermediate-to high-risk patients in both cohorts.CONCLUSION We constructed and validated a new prognostic model for variceal rebleeding with excellent predictive per-formance,which will improve the clinical management of rebleeding in EGVB patients.展开更多
Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in brea...Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies;(2) patients with breast cancer;(3) ctDNA measurement;(4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. Results: A total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50–0.83), with lower ORR in the ctDNA-positive group than ctDNAnegative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04–0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73–12.17;relapse outcome: RR = 7.11, 95% CI: 3.05–16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12–3.70;post-operative: HR = 6.03, 95% CI: 1.31–27.78). Conclusions: In this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.展开更多
BACKGROUND Sterol O-acyltransferase 1(SOAT1)is an important target in the diagnosis and treatment of liver cancer.However,the prognostic value of SOAT1 in patients with hepatocellular carcinoma(HCC)is still not clear....BACKGROUND Sterol O-acyltransferase 1(SOAT1)is an important target in the diagnosis and treatment of liver cancer.However,the prognostic value of SOAT1 in patients with hepatocellular carcinoma(HCC)is still not clear.AIM To investigate the correlation of SOAT1 expression with HCC,using RNA-seq and gene expression data of The Cancer Genome Atlas(TCGA)-liver hepatocellular carcinoma(LIHC)and pan-cancer.METHODS The correlation between SOAT1 expression and HCC was analyzed.Cox hazard regression models were conducted to investigate the prognostic value of SOAT1 in HCC.Overall survival and disease-specific survival were explored based on TCGA-LIHC data.Biological processes and functional pathways mediated by SOAT1 were characterized by gene ontology(GO)analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of differentially expressed genes.In addition,the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this malignancy.RESULTS SOAT1 and SOAT2 were highly expressed in unpaired samples,while only SOAT1 was highly expressed in paired samples.The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748,while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676.Patients with higher SOAT1 expression had lower survival rates.Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway,the IL-18 signaling pathway,the calcium signaling pathway,secreted factors,the Wnt signaling pathway,the Jak/STAT signaling pathway,the MAPK family signaling pathway,and cell–cell communication were involved in such association.SOAT1 expression was positively associated with the abundance of macrophages,Th2 cells,T helper cells,CD56bright natural killer cells,and Th1 cells,and negatively linked to the abundance of Th17 cells,dendritic cells,and cytotoxic cells.CONCLUSION Our findings demonstrate that SOAT1 may serve as a novel target for HCC treatment,which is helpful for the development of new strategies for immunotherapy and metabolic therapy.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is limited.AIM To analyze the impacts of stress granule(SG)genes on overall survival(OS)...BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is limited.AIM To analyze the impacts of stress granule(SG)genes on overall survival(OS),survival time,and prognosis in HCC.METHODS The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC),GSE25097,and GSE36376 datasets were utilized to obtain genetic and clinical information.Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach,and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression,respectively.The prognostic model’s receiver operating characteristic(ROC)curve was produced and plotted utilizing the time ROC software package.Nomogram models were constructed to predict the outcomes at 1,3,and 5-year OS prognostications with good prediction accuracy.RESULTS We identified seven SG genes(DDX1,DKC1,BICC1,HNRNPUL1,CNOT6,DYRK3,CCDC124)having a prognostic significance and developed a risk score model.The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group(P<0.001).The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort.Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle,RNA editing,and other biological processes.CONCLUSION Based on the impact of SG genes on HCC prognosis,in the future,it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.展开更多
Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper pos...Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.展开更多
BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the para...BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the paradoxical role of C.albicans in CRC,aiming to determine whether it promotes or suppresses tumor development,with a focus on the mechanistic basis linked to its metabolic profile.AIM To investigate the dual role of C.albicans in the development and progression of CRC through metabolite profiling and to establish a prognostic model that integrates the microbial and metabolic interactions in CRC,providing insights into potential therapeutic strategies and clinical outcomes.METHODSA prognostic model integrating C. albicans with CRC was developed, incorporating enrichment analysis, immuneinfiltration profiling, survival analysis, Mendelian randomization, single-cell sequencing, and spatial transcriptomics.The effects of the C. albicans metabolite mixture on CRC cells were subsequently validated in vitro. Theprimary metabolite composition was characterized using liquid chromatography-mass spectrometry.RESULTSA prognostic model based on five specific mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, wasestablished. The C. albicans metabolite mixture significantly reduced CRC cell viability. Post-treatment analysisrevealed a significant decrease in gene expression in HT29 cells, while the expression levels of TIMP1, EHD4, andGADD45B were significantly elevated in HCT116 cells. Conversely, LIME1 expression and that of other CRC celllines showed reductions. In normal colonic epithelial cells (NCM460), GADD45B, TIMP1, and FDFT1 expressionlevels were significantly increased, while LIME1 and EHD4 levels were markedly reduced. Following metabolitetreatment, the invasive and migratory capabilities of NCM460, HT29, and HCT116 cells were reduced. Quantitativeanalysis of extracellular ATP post-treatment showed a significant elevation (P < 0.01). The C. albicans metabolitemixture had no effect on reactive oxygen species accumulation in CRC cells but led to a reduction in mitochondrialmembrane potential, increased intracellular lipid peroxidation, and induced apoptosis. Metabolomic profilingrevealed significant alterations, with 516 metabolites upregulated and 531 downregulated.CONCLUSIONThis study introduced a novel prognostic model for CRC risk assessment. The findings suggested that the C.albicans metabolite mixture exerted an inhibitory effect on CRC initiation.展开更多
BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-...BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.展开更多
基金supported by Beijing Science and Technology Commission(grant number Z211100002921059)National Science and Technology Major Projects of China(2017ZX10201201-001-006,2017ZX10201201-002-006,and 2018ZX10715-005-003-005)+5 种基金Digestive Medical Coordinated Development Center of Beijing Hospital Authority(XXZ0302 and XXT28)National Key R&D Program China(2022YFC2603505)Beijing Hospital Authority Clinical Medicine Development with Special Funding Support(XMLX 202127)High-Level Public Health Technical Personnel Training Program of Beijing the Municipal Health Commission(2022-3-050)Capital Health Research and Development of Special(2022-1-2172)HBV infection,Clinical Cure and Immunology Joint Laboratory for Clinical Medicine Capital Medical University.
文摘Objective Hepatocellular carcinoma(HCC)is sensitive to ferroptosis,a new form of programmed cell death that occurs in most tumor types.However,the mechanism through which ferroptosis modulates HCC remains unclear.This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy.Methods Using clinicopathological parameters and bioinformatic techniques,we comprehensively examined the expression of FANCD2 macroscopically and microcosmically.We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death.Results FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration.As an independent risk factor for HCC,a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade.Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism.Conclusion To the best of our knowledge,this is the first study to comprehensively elucidate the oncogenic role of FANCD2.FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC;hence,it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
基金supported by a grant from the National Re-search Foundation of Korea(grant number:RS-2022-00165755).
文摘Background:Although the prognostic nutritional index(PNI)may predict surgical outcomes in certain cancers,the impact of PNI on surgical prognosis in patients undergoing pylorus-preserving pancreati-coduodenectomy(PPPD)is unclear.This study aimed to investigate the impact of preoperative PNI on mortality rate and cancer recurrence rate in patients who underwent PPPD.Methods:A total of 718 patients who were diagnosed with periampullary or pancreatic cancer and un-derwent PPPD between January 2012 and December 2016 were analyzed.Patients were categorized into two groups using the optimal cut-offvalue for PNI,determined by calculating the receiver operating characteristic(ROC)curve and the Youden index.We performed propensity score matching(PSM)anal-ysis to compare the mortality rate and cancer recurrence rate between the two groups.In addition,Cox regression analyses were performed to examine the association of PNI with mortality rate and cancer recurrence rate.Results:Using the 1-year mortality as an endpoint,the area under the ROC curve for PNI was 0.620(opti-mal cut-offvalue:41.7).We observed significant differences in 1-year(P=0.001),5-year(P=0.002),and overall(P=0.001)mortality;1-year(P=0.013),5-year(P=0.032),and overall(P=0.017)cancer re-currence between groups after PSM.High PNI was significantly associated with reduced 1-year[adjusted hazard ratio(HR)=0.44,95%confidence interval(CI):0.26-0.74,P=0.020],5-year(HR=0.66,95%CI:0.52-0.84,P<0.001),and overall(HR=0.71,95%CI:0.57-0.88,P=0.002)mortality;1-year(HR=0.70,95%CI:0.52-0.93,P=0.016),5-year(HR=0.78,95%CI:0.62-0.97,P=0.027)and overall(HR=0.78,95%CI:0.63-0.97,P=0.024)cancer recurrence.Conclusions:Preoperative PNI may serve as an independent factor for short-and long-term surgical prog-nosis in cancer patients undergoing PPPD.
基金funded by theGuangzhou Municipal Science and Tech-nology Bureau(No.2023A03J0507).
文摘Background:Lung cancer is the leading cause of cancer-related mortality,and while low-dose computed tomography screening may reduce mortality,emerging prognostic models show superior discriminative efficacy compared to age-and smoking history-based screening.However,further research is needed to assess their reliability in predicting lung cancer risk in high-risk patients.Methods:This study evaluated the predictive performance and quality of existing lung cancer prognostic models through a systematic review and meta-analysis.A comprehensive search was conducted in PubMed,Cochrane,Web of Science,CNKI,and Wanfang for articles published between January 1,2000,and February 13,2025,identifying population-basedmodels incorporating all available modeling data.Results:Among 72 analyzed studies,models were developed from Asian(28 studies,including 23 Chinese cohorts)and European/American(48 studies)populations,with only 6 focusing on nonsmokers.Twenty-one models included genetic markers,15 used clinical factors,and 40 integrated epidemiological predictors.Although 37 models underwent external validation,only 4 demonstrated minimal bias and clinical applicability.A meta-analysis of 11 repeatedly validated models revealed calibration and discrimination,though some lacked calibration data.Conclusions:Few lung cancer prognostic models exist for nonsmokers.Most models exhibit poor predictive performance in external validations,with significant bias and limited application scope.Widespread external validation,standardized model development,and reporting techniques are needed to accurately identify high-risk individuals and ensure applicability across diverse populations.
基金Supported by Seoul National University Bundang Hospital Research Fund,No.06-2021-0140National Research Foundation of Korea,No.RS-2024-00335454.
文摘BACKGROUND Among all solid tumors,pancreatic ductal adenocarcinoma(PDAC)is charac-terized by markedly poor survival outcomes,reflecting its high lethality,primarily as a result of late-stage diagnosis and limited treatment options.Pancreatic adenocarcinoma upregulated factor(PAUF)displays elevated expression in PDAC compared to non-neoplastic pancreatic samples and is involved in promoting tumor development.However,its exact diagnostic and prognostic significance remains unclear.This study aimed to assess the clinical relevance of PAUF expression in PDAC.We hypothesized that higher PAUF expression is associated with more aggressive clinicopathological features and poorer patient outcomes.AIM To investigate the expression of PAUF in PDAC and its value as a diagnostic and prognostic biomarker.METHODS PAUF expression levels were assessed using immunohistochemistry in tumor tissues from 93 patients with PDAC.Staining intensity and the proportion of tumor cells showing PAUF positivity were assessed to categorize patients into low and high PAUF expression groups.Associations between PAUF expression and clinicopathological characteristics or survival outcomes were analyzed.Public datasets(The Cancer Genome Atlas,Genotype-Tissue Expression,and Clinical Proteomic Tumor Analysis Consortium)were employed to validate differences in PAUF expression in PDAC at mRNA and protein levels.RESULTS PAUF expression was observed in 82.8%of samples,primarily localized within the cytoplasm of tumor cells.High PAUF expression showed a significant correlation with metastasis to lymph nodes(78.4%,P=0.0019),indicating a strong association with advanced disease.Public datasets confirmed elevated PAUF levels at both transcript and protein levels in PDAC relative to normal tissue.Kaplan-Meier estimates indicated that higher PAUF levels were linked with shorter overall survival(18.4 months vs 32.7 months,P=0.032).Multivariate Cox regression confirmed high PAUF expression as a prognostically significant variable contributing to poor clinical outcomes[hazard ratio(HR)=2.05;P=0.009].Poor tumor differentiation(HR=2.47;P=0.004)and lack of adjuvant therapy(HR=0.39;P=0.001)were also independently associated with unfavorable outcomes.CONCLUSION PAUF is a promising biomarker for tumor progression and prognosis in PDAC,with potential clinical utility in early diagnosis and the development of targeted therapies.
基金the Clinical Medical Team Introduction Program of Suzhou,No.SZYJTD201804.
文摘BACKGROUND Lymph node status is a critical prognostic factor in gastric cancer(GC),but stage migration may occur in pathological lymph nodes(pN)staging.To address this,alternative staging systems such as the positive lymph node ratio(LNR)and log odds of positive lymph nodes(LODDS)were introduced.AIM To assess the prognostic accuracy and stratification efficacy of three nodal staging systems in GC.METHODS A systematic review identified 12 studies,from which hazard ratios(HRs)for overall survival(OS)were summarized.Sensitivity analyses,subgroup analyses,publication bias assessments,and quality evaluations were conducted.To enhance comparability,data from studies with identical cutoff values for pN,LNR,and LODDS were pooled.Homogeneous stratification was then applied to generate Kaplan-Meier(KM)survival curves,assessing the stratification efficacy of three staging systems.RESULTS The HRs and 95%confidence intervals for pN,LNR,and LODDS were 2.16(1.72-2.73),2.05(1.65-2.55),and 3.15(2.15-4.37),respectively,confirming all three as independent prognostic risk factors for OS.Comparative analysis of HRs demonstrated that LODDS had superior prognostic predictive power over LNR and pN.KM curves for pN(N0,N1,N2,N3a,N3b),LNR(0.1/0.2/0.5),and LODDS(-1.5/-1.0/-0.5/0)revealed significant differences(P<0.001)among all prognostic stratifications.Mean differences and standard deviations in 60-month relative survival were 27.93%±0.29%,41.70%±0.30%,and 26.60%±0.28%for pN,LNR,and LODDS,respectively.CONCLUSION All three staging systems are independent prognostic factors for OS.LODDS demonstrated the highest specificity,making it especially useful for predicting outcomes,while pN was the most effective in homogeneous stratification,offering better patient differentiation.These findings highlight the complementary roles of LODDS and pN in enhancing prognostic accuracy and stratification.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.32070616 and 82170794).
文摘Background:Small ubiquitin-like modifier(SUMO)-specific proteases(SENPs)cleave the isopeptidic bond between SUMO1/2/3 and protein substrates,thus regulating the structure,activity,and lifetime of a variety of proteins.Recently,accumulating evidence has suggested that SENPs play a role in the initiation and progression of human cancers.Nevertheless,the potential role of the SENP family of proteins in liver cancer has yet to be fully elucidated.Methods:This study conducted a comprehensive bioinformatics analysis of the SENP family in liver cancer,including differential expression profiling,survival analysis,mutation and copy number variations(CNVs)assessment,immune infiltration and drug sensitivity correlation,functional enrichment analyses using data from The Cancer Genome Atlas(TCGA),Clinical Proteomic Tumor Analysis Consortium(CPTAC),LinkedOmics,and other public databases.Furthermore,we performed in vitro experiments using Huh-7 and Hep-3B cell lines to investigate the functional roles of SENP1 and SENP3 in hepatocellular carcinoma cell proliferation,colony formation,and migration.Results:Our results indicated that SENP1,3,and 7 were significantly overexpressed in liver hepatocellular carcinoma(LIHC).Elevated expressions of SENP1,3,and 7 are positively correlated with poor overall survival(OS)in LIHC patients.In addition,SENP1,3,and 7 expressions are related to immune infiltration and drug sensitivity.SENP1,3,and 7 co-expressed genes were enriched in mitochondrial function,ribosomal translation,and cell cycle control.Conclusion:SENP1,3,and 7 are prognostic biomarkers and potential therapeutic targets for LIHC.Knockdown of SENP1 and SENP3 inhibited the proliferation,clonogenicity,and migration of hepatocellular carcinoma cells.
基金Supported by the Science and Technology Program of Gansu Province,No.23JRRA1015the International Science and Technology Cooperation Project of Gansu Provincial Science and Technology Department,No.2023YFWA0009the Innovation and Entrepreneurship Project for Young Talents of Lanzhou Science and Technology Bureau,No.2023-4-18.
文摘BACKGROUND Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6),a member of the ENTPD family,has been implicated in certain cancers,yet a comprehensive analysis across multiple cancer types remains lacking.AIM To systematically evaluate ENTPD6’s expression,prognostic significance,and functions across multiple cancer types.METHODS In this study,we performed a pan-cancer analysis to investigate the correlation between ENTPD6 expression and various factors,including prognosis,genetic alterations,epigenetic modification,immune infiltration,immunotherapy responses,functional enrichment,and drug sensitivity.A tissue microarray of gastrointestinal tumors was used to validate differential ENTPD6 protein expression.RESULTS Pan-cancer analysis revealed that ENTPD6 expression was significantly elevated in many cancers.Immunohistochemistry staining analysis revealed that ENTPD6 expression was significantly higher in esophageal carcinoma,stomach adenocarcinoma,colon adenocarcinoma,rectal adenocarcinoma,and pancreatic adenocarcinoma compared to normal tissues.Furthermore,ENTPD6 expression was strongly associated with immune-infiltrating cells,particularly clusters of differentiation 8+T cells and natural killer cells,and correlated with immune-related genomic features including tumor mutational burden and microsatellite instability.Pathway analysis indicated that ENTPD6 expression was primarily linked to purine and pyrimidine metabolism pathways.Drug sensitivity analysis revealed that high ENTPD6 expression was sensitive to RDEA119,selumetinib,and PD-0325901.CONCLUSION This pan-cancer study elucidates the pivotal role of ENTPD6 in tumor progression and establishes its potential as a therapeutic target for immunotherapeutic approaches in specific malignancies.
基金Our study has been approved by Medical Research Ethics Approval Committee(2023010122HN11C).
文摘BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence(P=0.030).The ROC curve indicated that Treg+Ki-67+age(≥65 years)combined could predict irAEs well(area under the curve=0.753,95%confidence interval:0.623-0.848,P=0.001).Results of the Kaplan-Meier survival curve showed that progressionfree survival(PFS)was longer in the irAEs group than in the non-irAEs group(P=0.001).Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS(P=0.006).CONCLUSION The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy.irAEs can affect the patients’PFS and result in longer PFS.Treg+Ki-67+age(≥65 years old)combined can better predict the occurrence of adverse reactions.
文摘Background: Studies of gastrointestinal (GIT) cancers have shown that circZFR could be involved in the development and progression of various GIT cancers. However, small sample sizes limit the clinical significance of these studies. Here, a meta-analysis was conducted to ascertain the actual involvement of circZFR in the development and prognosis of GIT cancers. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched up to December 31, 2023. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to evaluate the association between circZFR expression and overall survival (OS). Publication bias was measured using the funnel plot and Egger’s test. Results: 10 studies having 659 participants were enrolled for meta-analysis. High circZFR expression was associated with poor OS (HR = 1.4, 95% CI: 1.20, 1.70). High circZFR expression also predicted larger tumor size (OR = 4.38, 95% CI 2.65, 7.25), advanced clinical stage (OR = 5.33, 95% CI 3.10, 9.16), and tendency for distant metastasis (OR = 2.89, 95% CI: 1.62, 5.11), but was not related to age, gender, and histological grade. Conclusions: In summary, high circZFR expression was associated with poor OS, larger tumor size, advanced stage cancer and tendency for distant metastasis. These findings suggested that circZFR could be a prognostic marker for GIT cancers.
基金supported by Achievement Transformation Project(No.CGZH21001)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21007)+4 种基金Translational Research Grant of NCRCH(No.2021WWB03)Chengdu Science and Technology Program(No.2022-YF05-01444-SN)Key Research and Development Program of Sichuan Province(No.2023YFS0031)National Key Research and Development Program of China(Nos.2022YFC2502600,2022YFC2502603)National Natural Science Foundation of China(No.82370192).
文摘Background:Dihydrolipoamide S-acetyltransferase(DLAT)is a subunit of the pyruvate dehydrogenase complex(PDC),a rate-limiting enzyme complex,that can participate in either glycolysis or the tricarboxylic acid cycle(TCA).However,the pathogenesis is not fully understood.We aimed to perform a more systematic and comprehensive analysis of DLAT in the occurrence and progression of tumors,and to investigate its function in patients’prognosis and immunotherapy.Methods:The differential expression,diagnosis,prognosis,genetic and epigenetic alterations,tumor microenvironment,stemness,immune infiltration cells,function enrichment,single-cell analysis,and drug response across cancers were conducted based on multiple computational tools.Additionally,we validated its carcinogenic effect and possible mechanism in glioma cells.Results:We exhibited that DLAT expression was increased in most tumors,especially in glioma,and affected the survival of tumor patients.DLAT was related to RNA modification genes,DNA methylation,immune infiltration,and immune infiltration cells,including CD4+T cells,CD8+T cells,Tregs,and cancer-associatedfibroblasts.Single-cell analysis displayed that DLAT might regulate cancer by mediating angiogenesis,inflammation,and stemness.Enrichment analysis revealed that DLAT might take part in the cell cycle pathway.Increased expression of DLAT leads tumor cells to be more resistant to many kinds of compounds,including PI3Kβinhibitors,PKC inhibitors,HSP90 inhibitors,and MEK inhibitors.In addition,glioma cells with DLAT silence inhibited proliferation,migration,and invasion ability,and promoted cell apoptosis.Conclusion:We conducted a comprehensive analysis of DLAT in the occurrence and progression of tumors,and its possible functions and mechanisms.DLAT is a potential diagnostic,prognostic,and immunotherapeutic biomarker for cancer patients.
基金Guizhou Provincial Department of Science and Technology Natural Science Foundation(No Foundation-ZK[2022])the Guizhou Provincial Health Commission Science and Technology Fund(No.GZWKJ2023-135)the Science Foundation of 925th Hospital(No.2023[3],No.2022[3/4]).
文摘Background:The cyclin-dependent kinase inhibitor 2a(CDKN2A)gene,identified as the multiple tumor suppressor gene,functions as a regulatory gene implicated in cancer pathogenesis.Its significance lies in its pivotal involvement in the genesis of various tumors;notwithstanding,the precise connection between CDKN2A and c olon adenocarcinoma(COAD)remains undisclosed.Methods:The objective of this research was to assess the predictive importance of CDKN2A in COAD by analyzing data from The Cancer Genome Atlas database.Logistic regression,signed rank test,Wilcoxon test,and Kruskal-Wallis test were used to examine CDKN2A expression levels and clinicopathological features.Univariate and multivariate Cox r egression analyses and Kaplan-Meier analysis found prognostic variables.Additionally,gene set enrichment analysis identified key CDKN2A expression pathways.The study additionally examined CDKN2A expression with tumor immune infiltration using The Cancer Genome Atlas data and single sample gene set enrichment analysis.Results:The results of this investigation indicated a substantial connection between higher CDKN2A expression and negative outcomes in terms of overall survival and disease-related survival among COAD patients.Gene set enrichment analysis indicated a tight link between CDKN2A and both the cell cycle and hedgehog signaling pathways.Subsequent evaluation employing single sample gene set enrichment analysis demonstrated a positive link between CDKN2A expression with infiltration by iDCs,whereas a negative correlation was detected with infiltration by helper T cells.Conclusion:In conclusion,the present study gives strong data supporting the predictive value of CDKN2A and its possible usefulness as a biomarker for COAD.Additionally,our results show a reasonable link between CDKN2A expression and immune influx in COAD,putting light on the role of CDKN2A in the control of the tumor microenvironment.Nevertheless,additional studies are needed to confirm the underlying mechanisms of these relationships and to discover the therapeutic possibilities of targeting CDKN2A in the treatment of COAD.
基金National Natural Science Foundation of China,No.82360477 and No.82060539Natural Science Foundation of Hubei Province of China,No.2022CFB344+1 种基金the Scientific and Technological Project of Enshi Tujia and Miao Autonomous Prefecture of Hubei Province,No.D20220059“Selenium Engineering”Science and Technology Project of Enshi Tujia and Miao Autonomous Prefecture of Hubei Province,No.D20230071.
文摘BACKGROUND In recent studies,accumulating evidence has revealed a strong association between the inflammatory response and the prognosis of many tumors.There is a certain correlation of neutrophil-to-lymphocyte ratio(NLR)with the prognosis in gastric cancer(GC)patients undergoing neoadjuvant chemotherapy(NAC).However,the existing research results have remained controversial.AIM To explore the relationship between NLR ratio and prognosis of GC patients receiving NAC.METHODS A thorough systematic search was performed in databases such as PubMed,Embase,Web of Science,and Cochrane Library,the search is available until February 29,2024,and studies exploring the interaction of NLR with clinical outcomes were collected.Relevant studies meeting pre-defined inclusion and exclusion criteria were carefully chosen.The outcomes included progression-free survival(PFS),relapse-free survival,disease-free survival(DFS),and overall survival(OS).The hazard ratio(HR)and its corresponding 95%confidence interval(CI)were utilized for estimation.RESULTS Our analysis encompassed 852 patients and incorporated data from 12 cohort studies.The comprehensive analysis revealed a significant association of high NLR with reduced OS(HR=1.76;95%CI:1.22-2.54,P=0.003),relapsefree survival(HR=3.73;95%CI:1.74-7.96,P=0.0007),and PFS(HR=2.32;95%CI:1.42-3.81,P=0.0008)in patients.However,this correlation in disease-free survival was not significant.NLR demonstrated its crucial role in effectively predicting the OS of GC patients undergoing NAC at different detection times,ages,regions,and NLR thresholds.CONCLUSION In GC patients receiving NAC,an elevated NLR is strongly associated with reduced OS and PFS.NLR has become an effective biomarker for patient prognosis evaluation,providing valuable insights for the treatment strategies of NAC in GC patients.
基金Supported by Guangxi Health Department Scientific Research Program,No.Z20200206Project of Guangxi Liuzhou Science and Technology Bureau,No.2024YB0101B010。
文摘BACKGROUND Traditional methods cannot clearly visualize esophageal cancer(EC)tumor contours and metastases,which limits the clinical application of da Vinci robotassisted surgery.AIM To investigate the efficacy of the da Vinci robot in combination with nanocarbon lymph node tracers in radical surgery of EC.METHODS In total,104 patients with early-stage EC who were admitted to Liuzhou worker's Hospital from January 2020 to June 2023 were enrolled.The patients were assigned to an observation group(n=52),which underwent da Vinci robot-assisted minimally invasive esophagectomy(RAMIE)with the intraoperative use of nanocarbon tracers,and a control group(n=52),which underwent traditional surgery treatment.The operation time,intraoperative blood loss,postoperative drainage tube indwelling time,hospital stay,number of lymph nodes dissected,incidence of complications,and long-term curative effects were comparatively analyzed.The postoperative stress response C-reactive protein(CRP),cortisol,epinephrine(E)and inflammatory response interleukin(IL)-6,IL-8,IL-10,and tumor necrosis factor-alpha(TNF-α)were evaluated.RESULTS Compared with the control group,the observation group had significantly lower postoperative CRP,cortisol,and E levels(P<0.05)with a milder inflammatory response,as indicated by lower IL-6,IL-10,and TNF-αlevels(P<0.05).Patients who underwent RAMIE had less intraoperative blood loss and shorter operation times and hospital stays than those who underwent traditional surgery.The average number of dissected lymph nodes,time of lymph node dissection,and mean smallest lymph node diameter were all significantly lower in the observation group(P<0.05).The rate of postoperative complications was 5.77%in the observation group,significantly lower than the 15.38%observed in the control group.Furthermore,the lymphatic metastasis rate,reoperation rate,and 12-and 24-month cumulative mortality in the observation group were 1.92%,0%,0%,and 0%,respectively,all of which were significantly lower than those in the control group(P<0.05).CONCLUSION The treatment of EC using the da Vinci robot combined with nanocarbon lymph node tracers can achieve good surgical outcomes and demonstrates promising clinical applications.
基金Supported by National Natural Science Foundation of China,No.81874390 and No.81573948Shanghai Natural Science Foundation,No.21ZR1464100+1 种基金Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission,No.22S11901700the Shanghai Key Specialty of Traditional Chinese Clinical Medicine,No.shslczdzk01201.
文摘BACKGROUND Rebleeding after recovery from esophagogastric variceal bleeding(EGVB)is a severe complication that is associated with high rates of both incidence and mortality.Despite its clinical importance,recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are lacking.AIM To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal rebleeding.METHODS This study included 477 EGVB patients across 2 cohorts:The derivation cohort(n=322)and the validation cohort(n=155).The primary outcome was rebleeding events within 1 year.The least absolute shrinkage and selection operator was applied for predictor selection,and multivariate Cox regression analysis was used to construct the prognostic model.Internal validation was performed with bootstrap resampling.We assessed the discrimination,calibration and accuracy of the model,and performed patient risk stratification.RESULTS Six predictors,including albumin and aspartate aminotransferase concentrations,white blood cell count,and the presence of ascites,portal vein thrombosis,and bleeding signs,were selected for the rebleeding event prediction following endoscopic treatment(REPET)model.In predicting rebleeding within 1 year,the REPET model ex-hibited a concordance index of 0.775 and a Brier score of 0.143 in the derivation cohort,alongside 0.862 and 0.127 in the validation cohort.Furthermore,the REPET model revealed a significant difference in rebleeding rates(P<0.01)between low-risk patients and intermediate-to high-risk patients in both cohorts.CONCLUSION We constructed and validated a new prognostic model for variceal rebleeding with excellent predictive per-formance,which will improve the clinical management of rebleeding in EGVB patients.
基金funded by the Capital’s Funds for Health Improvement and Research(grant number:2024-1G-4023)the Special Project for Director,China Center for Evidence Based Traditional Chinese Medicine(grant number:2020YJSZX-2)the National Natural Science Foundation of China(grant number:72074011).
文摘Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies;(2) patients with breast cancer;(3) ctDNA measurement;(4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. Results: A total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50–0.83), with lower ORR in the ctDNA-positive group than ctDNAnegative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04–0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73–12.17;relapse outcome: RR = 7.11, 95% CI: 3.05–16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12–3.70;post-operative: HR = 6.03, 95% CI: 1.31–27.78). Conclusions: In this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.
基金Supported by the Tianjin Municipal Project of Science and Technology,No.21ZXGWSY00040and the Tianjin Health Research Project,No.TJWJ2022QN043.
文摘BACKGROUND Sterol O-acyltransferase 1(SOAT1)is an important target in the diagnosis and treatment of liver cancer.However,the prognostic value of SOAT1 in patients with hepatocellular carcinoma(HCC)is still not clear.AIM To investigate the correlation of SOAT1 expression with HCC,using RNA-seq and gene expression data of The Cancer Genome Atlas(TCGA)-liver hepatocellular carcinoma(LIHC)and pan-cancer.METHODS The correlation between SOAT1 expression and HCC was analyzed.Cox hazard regression models were conducted to investigate the prognostic value of SOAT1 in HCC.Overall survival and disease-specific survival were explored based on TCGA-LIHC data.Biological processes and functional pathways mediated by SOAT1 were characterized by gene ontology(GO)analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of differentially expressed genes.In addition,the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this malignancy.RESULTS SOAT1 and SOAT2 were highly expressed in unpaired samples,while only SOAT1 was highly expressed in paired samples.The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748,while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676.Patients with higher SOAT1 expression had lower survival rates.Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway,the IL-18 signaling pathway,the calcium signaling pathway,secreted factors,the Wnt signaling pathway,the Jak/STAT signaling pathway,the MAPK family signaling pathway,and cell–cell communication were involved in such association.SOAT1 expression was positively associated with the abundance of macrophages,Th2 cells,T helper cells,CD56bright natural killer cells,and Th1 cells,and negatively linked to the abundance of Th17 cells,dendritic cells,and cytotoxic cells.CONCLUSION Our findings demonstrate that SOAT1 may serve as a novel target for HCC treatment,which is helpful for the development of new strategies for immunotherapy and metabolic therapy.
基金Supported by Hebei Traditional Chinese Medicine Scientific Research Project,No.2023223.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is limited.AIM To analyze the impacts of stress granule(SG)genes on overall survival(OS),survival time,and prognosis in HCC.METHODS The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC),GSE25097,and GSE36376 datasets were utilized to obtain genetic and clinical information.Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach,and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression,respectively.The prognostic model’s receiver operating characteristic(ROC)curve was produced and plotted utilizing the time ROC software package.Nomogram models were constructed to predict the outcomes at 1,3,and 5-year OS prognostications with good prediction accuracy.RESULTS We identified seven SG genes(DDX1,DKC1,BICC1,HNRNPUL1,CNOT6,DYRK3,CCDC124)having a prognostic significance and developed a risk score model.The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group(P<0.001).The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort.Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle,RNA editing,and other biological processes.CONCLUSION Based on the impact of SG genes on HCC prognosis,in the future,it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.
基金Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.
基金Supported by Gansu Province Joint Fund General Program,No.24JRRA878Gansu Provincial Science and Technology Program Project,No.24JRRA1020+2 种基金Gansu Province Key Talent Program,No.2025RCXM006Teaching Research and Reform Program for Postgraduate Education at Gansu University of Traditional Chinese Medicine(GUSTCM),No.YBXM-202406Special Fund for Mentors of“Qihuang Talents”in the First-Level Discipline of Chinese Medicine,No.ZYXKBD-202415。
文摘BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the paradoxical role of C.albicans in CRC,aiming to determine whether it promotes or suppresses tumor development,with a focus on the mechanistic basis linked to its metabolic profile.AIM To investigate the dual role of C.albicans in the development and progression of CRC through metabolite profiling and to establish a prognostic model that integrates the microbial and metabolic interactions in CRC,providing insights into potential therapeutic strategies and clinical outcomes.METHODSA prognostic model integrating C. albicans with CRC was developed, incorporating enrichment analysis, immuneinfiltration profiling, survival analysis, Mendelian randomization, single-cell sequencing, and spatial transcriptomics.The effects of the C. albicans metabolite mixture on CRC cells were subsequently validated in vitro. Theprimary metabolite composition was characterized using liquid chromatography-mass spectrometry.RESULTSA prognostic model based on five specific mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, wasestablished. The C. albicans metabolite mixture significantly reduced CRC cell viability. Post-treatment analysisrevealed a significant decrease in gene expression in HT29 cells, while the expression levels of TIMP1, EHD4, andGADD45B were significantly elevated in HCT116 cells. Conversely, LIME1 expression and that of other CRC celllines showed reductions. In normal colonic epithelial cells (NCM460), GADD45B, TIMP1, and FDFT1 expressionlevels were significantly increased, while LIME1 and EHD4 levels were markedly reduced. Following metabolitetreatment, the invasive and migratory capabilities of NCM460, HT29, and HCT116 cells were reduced. Quantitativeanalysis of extracellular ATP post-treatment showed a significant elevation (P < 0.01). The C. albicans metabolitemixture had no effect on reactive oxygen species accumulation in CRC cells but led to a reduction in mitochondrialmembrane potential, increased intracellular lipid peroxidation, and induced apoptosis. Metabolomic profilingrevealed significant alterations, with 516 metabolites upregulated and 531 downregulated.CONCLUSIONThis study introduced a novel prognostic model for CRC risk assessment. The findings suggested that the C.albicans metabolite mixture exerted an inhibitory effect on CRC initiation.
基金supported by Beijing Natural Science Foundation(No.7222162 to Dr.Hui Liu)。
文摘BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.
