Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integ...Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.展开更多
BACKGROUND Gastric adenocarcinoma with primitive phenotypes has recently attracted increasing attention due to its aggressive nature and challenging diagnosis.Gastric adenocarcinoma with enteroblastic differentiation(...BACKGROUND Gastric adenocarcinoma with primitive phenotypes has recently attracted increasing attention due to its aggressive nature and challenging diagnosis.Gastric adenocarcinoma with enteroblastic differentiation(GAED)and hepatoid adenocarcinoma(HAC)were previously regarded as gastric adenocarcinoma with primitive enterocyte phenotype(GAPEP).GAPEP is known for its poor prognosis,and the accurate diagnosis of GAPEP directly affects therapeutic decision-making.Despite their poor prognosis and morphological heterogeneity,the molecular drivers of GAPEP,particularly methylation-driven mechanisms,remain poorly explored.AIM To investigate the clinicopathological and molecular characteristics of GAPEP and establish an integrative diagnostic strategy to guide therapeutic decision-making.METHODS Based on the expression profile and morphology,patients were divided into three groups:GAPEP(including GAED and HAC),conventional gastric cancer(CGC),and CGC expressing primitive phenotypic markers.We analyzed clinicopathological features and overall survival.Data from The Cancer Genome Atlas were also analyzed,and functional enrichment analysis was conducted.RESULTS GAPEP showed diverse morphology,and immunohistochemical staining alone was not adequate for accurate diagnosis.Histologically,GAPEP was characterized by large,polygonal tumor cells with supranuclear or subnuclear vacuoles,a“piano keyboard-like”appearance,and clear or eosinophilic cytoplasms.Compared to CGC and CGC expressing primitive phenotypic markers,GAPEP displayed more aggressive clinical features.Molecular analysis showed significant differences in molecular subtypes,TP53 mutation,ERBB2 amplification,ARID1A mutation,MSI status,and CpG island methylator phenotype category.Genomic analysis revealed that TP53 mutations,APC mutations,and ERBB2 amplifications were more frequent in GAPEP.Genes involved in methylation processes were highly upregulated in GAPEP.HAC and GAED shared similar clinicopathological and genetic characteristics.Functional enrichment analysis highlighted the critical role of methylation in the development of GAPEP.CONCLUSION The diversity and aggressiveness of GAPEP are driven by deregulated methylation,necessitating the integration of morphological and immunohistochemical diagnosis.Targeting methylation can provide new therapeutic opportunities for treating this aggressive cancer.展开更多
BACKGROUND Mesonephric-like adenocarcinoma(MLA)is a rare and highly malignant disease that occurs in the uterine body or ovaries.We report a case of a MLA that was considered to have originated in the fallopian tube a...BACKGROUND Mesonephric-like adenocarcinoma(MLA)is a rare and highly malignant disease that occurs in the uterine body or ovaries.We report a case of a MLA that was considered to have originated in the fallopian tube and presented with malignant peritonitis.CASE SUMMARY A 57-year-old female presented with a chief complaint of abdominal pain that began 2 months prior.Cancerous peritonitis was suspected.During exploratory laparoscopy,the right fallopian tube was found to be enlarged,with widespread disseminated lesions extending from the pelvic cavity to the upper abdomen.Histopathological examination of the peritoneal tissue obtained by biopsy showed tumor cells with a high nuclear/cellular ratio and proliferation of papillary tubular to pedunculated solid nests.Immunohistochemical testing was positive for GATA-binding protein 3,thyroid transcription factor 1,cluster of differentiation 10,and paired box protein-8,and negative for estrogen receptor,Wilms’tumor 1,and wild-type p53,leading to the diagnosis of MLA.Subsequently,debulking surgery was performed,and no macroscopic residual tumors were identified.The pathological diagnosis was right tubal carcinoma,mesonephric adenocarcinoma(International Federation of Gynecology and Obstetrics stage IIIC),and pT3cNXM0.Adjuvant chemotherapy was administered postoperatively;however,recurrence was noted,and the patient died 1 year and 6 months after the initial treatment.CONCLUSION MLA is a very rare disease with poor prognosis.Further studies are necessary to identify effective treatment options.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:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impa...Background:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impacts on LUAD prognosis using Gene Expression Profiling Interactive Analysis(GEPIA).Methods:Functional assays including CCK-8,wound-healing,5-ethynyl-2-deoxyuridine(EdU),Transwell assays,and flow cytometry,elucidated STIL and E2F1’s effects on cell viability,proliferation,apoptosis,and migration.Gene set enrichment analysis(GSEA)identified potential pathways,while metabolic assays assessed glucose metabolism.Results:Our findings reveal that STIL and E2F1 are overexpressed in LUAD,correlating with adverse outcomes.It enhances cell proliferation,migration,and invasion,and suppresses apoptosis,activating downstream of E2F1.Silencing E2F1 reversed the promotion effect of the STIL overexpression on cell viability and invasiveness.Importantly,STIL modulates glycolysis,influencing glucose consumption,lactate production,and energy balance in LUAD cells.Conclusion:Our model,incorporating STIL,age,and disease stage,robustly predicts patient prognosis,underscored STIL’s pivotal role in LUAD pathogenesis through metabolic reprogramming.This comprehensive approach not only confirms STIL’s prognostic value but also highlights its potential as a therapeutic target in LUAD.展开更多
Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surge...Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surgery.This study aimed to develop and validate a computed tomography(CT)-based radiomics and deep learning(DL)fusion model for predicting non-invasive OLNM.Methods:Patients with radiologically node-negative lung adenocarcinoma from two centers were retrospectively analyzed.We developed clinical,radiomics,and radiomics-clinical models using logistic regression.A DL model was established using a three-dimensional squeeze-and-excitation residual network-34(3D SE-ResNet34)and a fusion model was created by integrating seleted clinical,radiomics features and DL features.Model performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Five predictive models were compared;SHapley Additive exPlanations(SHAP)and Gradient-weighted Class Activation Mapping(Grad-CAM)were employed for visualization and interpretation.Results:Overall,358 patients were included:186 in the training cohort,48 in the internal validation cohort,and 124 in the external testing cohort.The DL fusion model incorporating 3D SE-Resnet34 achieved the highest AUC of 0.947 in the training dataset,with strong performance in internal and external cohorts(AUCs of 0.903 and 0.907,respectively),outperforming single-modal DL models,clinical models,radiomics models,and radiomicsclinical combined models(DeLong test:P<0.05).DCA confirmed its clinical utility,and calibration curves demonstrated excellent agreement between predicted and observed OLNM probabilities.Features interpretation highlighted the importance of textural characteristics and the surrounding tumor regions in stratifying OLNM risk.Conclusions:The DL fusion model reliably and accurately predicts OLNM in early-stage lung adenocarcinoma,offering a non-invasive tool to refine staging and guide personalized treatment decisions.These results may aid clinicians in optimizing surgical and radiotherapy strategies.展开更多
Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung ...Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung cancer potential.We aimed to explore the anti–lung cancer effect of BBR and related mechanisms by targeting the glycogen synthase kinase 3β(GSK3β)/β-catenin pathway.Methods:Lung adenocarcinoma(LUAD)cells A549 and NCI-H1975 were treated with BBR.Results:Our results showed that BBR inhibited cell proliferation by decreasing c-Myc levels and induced cel cycle arrest in the G0/G1 phase by lowering cyclin D1 levels.BBR induced apoptosis by upregulating cleaved caspase 3 levels.BBR inhibited cell migration and invasion by decreasing N-cadherin levels.Furthermore,BBR upregulated the expression of GSK3βprotein and phospho-β-catenin proteins in the cytoplasm,while decreasing the expression ofβ-catenin protein.Next,LUAD cel s were exposed to CHIR-99021(a GSK3βinhibitor).This treatment led to an increase in c-Myc,cyclin D1,andβ-catenin levels at specific concentrations.BBR partially reversed the effects of CHIR-99021.Finally,LUAD cells were treated with CHIR-99021(4μmoL/L)combined with BBR(30 and 60μmoL/L)for 24 h.The expression of programmed death ligand 1(PD-L1)was assessed by Western blot analysis.Jurkat T cells and A549 cel s were cocultured for 24 h to examine the lactate dehydrogenase release rate.Results suggested that BBR suppressed the expression of PD-L1 and heightened the immune lethality of T cells.Conclusions:BBR suppressed the proliferative activity of LUAD cell lines A549 and NCI-H1975 in vitro,induced cell cycle arrest and cancer cel apoptosis in the G0/G1 stage,and repressed the migration and invasion of cancer cells.BBR reduced the PD-L1 protein expression and enhanced T-cell–mediated cytotoxicity.These effects appear to be related to BBR's regulation of the GSK3β/β-catenin pathway.展开更多
Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was...Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.展开更多
BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram ...BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram using internal and external validation to predict survival in patients with ampullary adenocarcinoma.METHODS Data were sourced from the surveillance,epidemiology,and end results stat database.The patients in the database were randomized in a 7:3 ratio into training and validation groups.Using Cox regression univariate and multivariate analyses in the training group,we identified independent risk factors for overall survival and cancer-specific survival to develop the nomogram.The nomogram was validated with a cohort of patients from the First Affiliated Hospital of the Army Medical University.RESULTS For overall and cancer-specific survival,12(sex,age,race,lymph node ratio,tumor size,chemotherapy,surgical modality,T stage,tumor differentiation,brain metastasis,lung metastasis,and extension)and 6(age;surveillance,epidemiology,and end results stage;lymph node ratio;chemotherapy;surgical modality;and tumor differentiation)independent risk factors,respectively,were incorporated into the nomogram.The area under the curve values at 1,3,and 5 years,respectively,were 0.807,0.842,and 0.826 for overall survival and 0.816,0.835,and 0.841 for cancer-specific survival.The internal and external validation cohorts indicated good consistency of the nomogram.CONCLUSION The dynamic nomogram offers robust predictive efficacy for the overall and cancer-specific survival of ampullary adenocarcinoma.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment opti...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.展开更多
The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp...The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp.39–45.展开更多
In a recent study by He et al,the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen,thereby improving the accuracy of identifying high-risk patients c...In a recent study by He et al,the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen,thereby improving the accuracy of identifying high-risk patients compared to relying solely on preoperative markers,which has significant implications for customizing adjuvant therapy and potentially improving outcomes for this aggressive form of cancer.However,the study’s single-center design and short follow-up period may limit the generalizability of its findings and potentially introduce reporting bias.Future studies could consider additional confounding factors,such as adjuvant chemotherapy and variations in surgical techniques,to improve the model’s accuracy.Furthermore,it would be valuable to validate the nomogram in broader,prospective cohorts and explore the inclusion of additional markers like circulating tumor DNA to refine further its predictive power and applicability across diverse patient populations.展开更多
BACKGROUND Ileum adenocarcinoma(IA),a type of small bowel adenocarcinoma,is a rather uncommon factor associated with obstruction in small bowel.Owing to its location and indefinite clinical symptoms,the diagnosis of I...BACKGROUND Ileum adenocarcinoma(IA),a type of small bowel adenocarcinoma,is a rather uncommon factor associated with obstruction in small bowel.Owing to its location and indefinite clinical symptoms,the diagnosis of IA is difficult,and survival is usually poor.With respect to the rarity of this disease,very few studies have reported such cases to provide a reference for treatment.CASE SUMMARY In this manuscript,a case of a 48-year-old man presented with chronic right lower abdominal pain and distention,queasiness and emesis.A computed tomography scan revealed intestinal wall thickening and an intestinal obstruction in the terminal ileum.He was diagnosed with inflammatory bowel disease.However,his symptoms were not relieved after conservative treatment.The patient sub-sequently underwent exploratory laparotomy,and a tumour in the ileum measuring approximately 2.0 cm×2.0 cm that was located 20 cm from the ileocolic valve was discovered incidentally and was operatively resected along with the enlarged lymph nodes.Pathological examination revealed a stage IIA(T3N0M0)ulcerative IA.Along with imaging examinations,a diagnosis of primary IA with no lymph or distant metastases was considered.The patient was discharged and recovered well as of the writing of this manuscript.CONCLUSION IA should be considered as a differential diagnosis in cases of intestinal obstruction,and the recommended method for local disease treatment is surgery.展开更多
Objective:A highly aggressive and lethal malignancy,characterized by its heterogeneity,lung adenocarcinoma(LUAD)presents significant challenges in prognosis and treatment.Disulfidptosis,a newly identified form of regu...Objective:A highly aggressive and lethal malignancy,characterized by its heterogeneity,lung adenocarcinoma(LUAD)presents significant challenges in prognosis and treatment.Disulfidptosis,a newly identified form of regulated cell death,offers novel insights into cancer progression,yet its role in LUAD remains poorly understood.Methods:We identified disulfidptosis-related genes(DRGs)from prior studies and analyzed their interactions and functional enrichment.Molecular subtypes were identified through consensus clustering based on DRG expression,and a prognostic DRG signature was developed using multivariate Cox regression analysis.A nomogram integrating clinical variables was developed to predict survival.Comprehensive analyses,including single-cell RNA sequencing,immune infiltration,and drug sensitivity,were validated using clinical specimens,LUAD cell lines,Western blotting(WB)and immunohistochemistry(IHC).Results:A total of 16 DRGs were identified,classifying LUAD patients into three distinct subtypes with differential survival and immune profiles.A 4-gene signature(GYS1,NDUFA11,NDUFB10,SLC7A11)was used to build a risk score model,demonstrating robust prognostic accuracy.A nomogram combining this signature with clinical features reliably predicted 1-,3-,and 5-year survival.The signature correlated with immune cell infiltration,with single-cell analysis revealing DRG enrichment in myeloid cells.Notably,SLC7A11 and GYS1 were positively associated with chemotherapeutic drug sensitivity.Validation through reverse transcription quantitative polymerase chain reaction(RT-qPCR),WB and IHC confirmed upregulated DRG expression in LUAD tissues and cell lines.Conclusions:This research highlights the essential role of DRGs in modulating the tumor microenvironment,influencing therapeutic response,and determining the prognosis of LUAD.The risk model and nomogram,derived from DRG expression,offer robust tools for survival prediction and personalized treatment stratification,facilitating the development of disulfidptosis-targeted therapeutic strategies.展开更多
Background:Lung adenocarcinoma,the most prevalent lung cancer subtype,is increasingly diagnosed in non-smokers and females.The cell cycle regulator CDC20(Cell Division Cycle 20),a crucial activator of the Anaphase-Pro...Background:Lung adenocarcinoma,the most prevalent lung cancer subtype,is increasingly diagnosed in non-smokers and females.The cell cycle regulator CDC20(Cell Division Cycle 20),a crucial activator of the Anaphase-Promoting Complex/Cyclosome(APC/C),is frequently overexpressed in various cancers,including lung adenocarcinoma,and is implicated in tumorigenesis.Preclinical studies indicate that inhibiting the CDC20-APC/C signaling axis can enhance chemotherapy-induced apoptosis.Analysis of The Cancer Genome Atlas(TCGA)data confirms that elevated CDC20 expression in lung adenocarcinoma is significantly associated with poorer patient prognosis and correlates with immune cell infiltration.These collective findings highlight CDC20 as a promising prognostic biomarker and a potential novel therapeutic target for lung adenocarcinoma.Methods:We collected 539 patients with LUAD and 59 normal controls of clinical data from the Cancer Genome Atlas(TCGA)for bioinformatics analysis to investigate the role of CDC20 in LUAD and address the above questions.We evaluated the association between CDC20 expression and clinicopathological features using the Kruskal Wallis test and multivariate logistic regression.Prognostic values were assessed using Cox regression and Kaplan-Meier survival analyses.We further used single-sample gene set enrichment analysis(ssGSEA)to explore correlations between CDC20 expression and immune infiltration levels.Results:CDC20 expression in LUAD tissues was significantly higher than that in normal controls(p<0.001)and showed high diagnostic accuracy(AUC[area under the curve]=0.979).Kaplan-Meier analysis revealed that high CDC20 expression predicted poorer overall survival(OS;HR=1.47,95%CI:1.10–1.97,p=0.009),although no significant association emerged with progression-free interval(p=0.172).ssGSEA indicated a strong positive correlation between CDC20 and T helper 2 cell infiltration(R=0.764,p<0.001),but negative correlations with mast cells(R=−0.469,p<0.001)and eosinophils(R=−0.343,p<0.001).Functional enrichment analyses(Gene ontology/Kyoto Encyclopedia of Genes and Genomes[GO/KEGG])of CDC20-associated genes provided additional mechanistic insights.Conclusions:The significantly elevated expression of CDC20 in LUAD tissues,coupled with its high diagnostic accuracy(AUC=0.979),underscores its potential utility in differentiating LUAD from normal tissue.More importantly,the strong association between high CDC20 expression and poorer overall survival(OS)establishes its independent prognostic value for predicting adverse patient outcomes.Beyond its correlation with clinical parameters,our findings illuminate potential mechanisms underlying CDC20's oncogenic role.The distinct positive correlation with T helper 2(Th2)cell infiltration and negative correlations with mast cells and eosinophils suggest that CDC20 may actively shape an immunosuppressive tumor microenvironment,potentially facilitating tumor immune evasion and progression.Functional enrichment analyses of CDC20-coexpressed genes further support its involvement in key oncogenic pathways,including cell cycle regulation and mitotic processes.Collectively,this study not only validates CDC20 as a valuable prognostic factor but also provides novel mechanistic insights linking its overexpression to altered immune landscapes in LUAD.展开更多
Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma(LUAD)have been identified,the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear....Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma(LUAD)have been identified,the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear.Using spatial transcriptomics and single-cell RNA-sequencing data from multi-regional LUAD biopsies consisting of tumor core,tumor edge,and normal area,we sought to delineate the spatial heterogeneity and driving factors of cell colocalization.Two cancer cell sub-clusters(Cancer_c1 and Cancer_c2),associated with LUAD initiation and metastasis,respectively,exhibit distinct spatial distributions and immune cell colocalizations.In particular,Cancer_c1,enriched within the tumor core,could directly interact with B cells or indirectly recruit B cells through macrophages.Conversely,Cancer_c2 enriched within the tumor edge exhibits colocalization with CD8^(+)T cells.Collectively,our work elucidates the spatial distribution of cancer cell subtypes and their interaction with immune cells in the core and edge of LUAD,providing insights for developing therapeutic strategies for cancer intervention.展开更多
Background:The centrosome,a crucial cellular structure involved in the mitotic process of eukaryotic cells,plays a significant role in tumor progression by regulating the growth and differentiation of neoplastic cells...Background:The centrosome,a crucial cellular structure involved in the mitotic process of eukaryotic cells,plays a significant role in tumor progression by regulating the growth and differentiation of neoplastic cells.This makes the centrosome a promising target for therapeutic strategies in cancer treatment.Methods:Utilizing data from the TCGA database,we identified centrosome-related genes and constructed a prognostic model for 518 lung adenocarcinoma patients.Prognosis-associated genes were initially screened using univariate Cox regression,with overfitting minimized by applying LASSO regression to remove collinearity.Finally,a set of 12 genes was selected through multivariable Cox regression for inclusion in the prognostic model.Results:The model’s performance was assessed using ROC curve analysis,demonstrating a robust predictive ability with an AUC of 0.728 in the training group and 0.695 in the validation group.Differential expression analysis between high-risk(HRLAs)and low-risk(LRLAs)individuals was performed,followed by enrichment analyses using KEGG,GO,Progeny,GSVA,and GSEA.These analyses revealed significant differences in immune-related pathways between the two groups.Immune microenvironment assessment through ssGSEA and ESTIMATE indicated that individuals with poor prognosis exhibited lower immune,stromal,and ESTIMATE scores,along with higher tumor purity,suggesting an impaired immune microenvironment in HRLAs patients.Drug susceptibility analysis and molecular docking showed that HRLAs individuals were more responsive to docetaxel,emphasizing the therapeutic relevance of paclitaxel in this cohort.Conclusion:We successfully developed and validated a centrosome-associated gene-based prognostic model,offering clinicians valuable insights for improved decision-making and personalized treatment strategies.This model may facilitate the identification of high-risk patients and guide therapeutic interventions in lung adenocarcinoma.展开更多
Objective:The aim of the current study was to identify independent prognostic factors,evaluate differential adjuvant chemotherapy efficacy across clinicopathologic subgroups,and define adjuvant chemotherapy-sensitive ...Objective:The aim of the current study was to identify independent prognostic factors,evaluate differential adjuvant chemotherapy efficacy across clinicopathologic subgroups,and define adjuvant chemotherapy-sensitive populations.Methods:A retrospective analysis of 168 AAC patients undergoing curative pancreaticoduodenectomy(2011-2020)was performed.Cases were classified into intestinal(28.0%),pancreatobiliary(30.4%),and mixed subtypes(18.5%)per NCCN(v2.2025)criteria.Independent prognostic factors for AAC patients were identified through uni-and multi-variable Cox proportional hazards modeling and subgroup analyses were stratified by age range,gender,differentiation,T stage,N stage,BVI,TDs,and PNI.Results:The pancreatobiliary signature(HR=2.884,P<0.001)and BVI(HR=2.330,P=0.001)were independent poor prognostic factors.Adjuvant chemotherapy improved overall survival(OS)in the following AAC patients:T3-T4 stage(HR=0.485,P=0.050);N1-N2 stage(HR=0.365,P=0.008);and TD-positive(HR=0.401,P=0.026).The median OS increased from 22.3-51.3 months with adjuvant chemotherapy in TD-positive patients(P=0.019).TD positivity conferred a worse prognosis in BVI-negative subgroups(OS:HR=3.840,95%CI:2.058-7.166,P<0.001;and progression-free survival(PFS):HR=2.950,95%CI:1.550-5.617,P=0.002).Conclusions:The pancreatobiliary signature and BVI constitute critical high-risk pathologic features in AAC.TD status identified high-risk cohorts,thus enabling postoperative risk-stratified treatment strategies.In patients negative for pancreatobiliary signature or BVI,TD positivity predicted significantly worse survival.展开更多
Lysosomal dysfunction has been implicated in the progression of colon adenocarcinoma(COAD),yet the prognostic significance and therapeutic potential of lysosome-related genes(LRGs)remain underexplored.In this study,we...Lysosomal dysfunction has been implicated in the progression of colon adenocarcinoma(COAD),yet the prognostic significance and therapeutic potential of lysosome-related genes(LRGs)remain underexplored.In this study,we construct a 6-LRG-based prognostic risk stratification model(DPP7,ADAM8,CD1B,LRP2,ATP6V1C2,and PLAAT3)by integrating LASSO and Cox regression analyses.Stratifying patients based on median risk scores,we demonstrate that high-risk patients exhibit significantly worse clinical outcomes across the TCGA cohort and five independent GEO datasets.Furthermore,this panel outperforms 136 previously published models in terms of predictive accuracy for 1-,3-,and 5-year survival rates.Validation multiplex immunofluorescence using an in-house tissue microarray cohort confirms that the 6-LRG signature serves as an independent prognostic factor.Additionally,high-risk patients exhibit distinct immunosuppressive tumor microenvironment and aggressive malignancy characteristics.Functional depletion of DPP7 significantly inhibits tumor cell proliferation,migration,and metastasis in both in vitro and in vivo settings.Moreover,DPP7 silencing attenuates epithelialemesenchymal transition,as evidenced by the upregulation of E-cadherin and downregulation of N-cadherin,Vimentin,and Snail.In conclusion,this study establishes an LRG-based model for COAD prognostic prediction and nominates DPP7 as a promising therapeutic target for COAD treatment.展开更多
BACKGROUND Most non-small cell lung cancer patients have epidermal growth factor receptor(EGFR)activating mutations,such as exon 19 deletion and exon 21 replacement mutations.Osimertinib is a third-generation EGFR-tyr...BACKGROUND Most non-small cell lung cancer patients have epidermal growth factor receptor(EGFR)activating mutations,such as exon 19 deletion and exon 21 replacement mutations.Osimertinib is a third-generation EGFR-tyrosine kinase inhibitors ap-proved for the treatment of lung cancer patients carrying EGFR activating mu-tations.Osimertinib-induced interstitial lung disease(ILD)is a rare and poten-tially fatal pulmonary toxic manifestation of drug therapy.At present,there is no international consensus on the risks and treatment of the osimertinib-induced ILD.CASE SUMMARY We report a case of a 56-year-old woman who was diagnosed with lung adenocar-cinoma with lung hilum,mediastinal lymph nodes and brain metastases(T4N3-M1c stage IVB).The patient received targeted treatment with osimertinib after radiotherapy and chemotherapy.But she developed ILD after osimertinib treat-ment.Following active symptomatic treatment and hormone treatment,the lung injury alleviated.The patient was retreated with furmonertinib combined with prednisone and did not experience ILD again.So far,she has survived for 14 months without disease progression.CONCLUSION Retreatment with furmonertinib under prednisone could be considered as an effective therapeutic option after risk-benefit assessment for EGFR-mutant lung adenocarcinoma patients.展开更多
基金supported by grants from the Guangxi Natural Science Foundation(2024GXNSFAA010150)the Guangdong Basic and Applied Basic Research Foundation(2022A1515111167).
文摘Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.
基金Supported by the Startup Fund for Scientific Research,Fujian Medical University,No.2020QH1168Fujian Provincial Science and Technology Innovation Joint Funds,No.2024Y9023the Fujian Provincial Natural Science Foundation of China,No.2024J011644.
文摘BACKGROUND Gastric adenocarcinoma with primitive phenotypes has recently attracted increasing attention due to its aggressive nature and challenging diagnosis.Gastric adenocarcinoma with enteroblastic differentiation(GAED)and hepatoid adenocarcinoma(HAC)were previously regarded as gastric adenocarcinoma with primitive enterocyte phenotype(GAPEP).GAPEP is known for its poor prognosis,and the accurate diagnosis of GAPEP directly affects therapeutic decision-making.Despite their poor prognosis and morphological heterogeneity,the molecular drivers of GAPEP,particularly methylation-driven mechanisms,remain poorly explored.AIM To investigate the clinicopathological and molecular characteristics of GAPEP and establish an integrative diagnostic strategy to guide therapeutic decision-making.METHODS Based on the expression profile and morphology,patients were divided into three groups:GAPEP(including GAED and HAC),conventional gastric cancer(CGC),and CGC expressing primitive phenotypic markers.We analyzed clinicopathological features and overall survival.Data from The Cancer Genome Atlas were also analyzed,and functional enrichment analysis was conducted.RESULTS GAPEP showed diverse morphology,and immunohistochemical staining alone was not adequate for accurate diagnosis.Histologically,GAPEP was characterized by large,polygonal tumor cells with supranuclear or subnuclear vacuoles,a“piano keyboard-like”appearance,and clear or eosinophilic cytoplasms.Compared to CGC and CGC expressing primitive phenotypic markers,GAPEP displayed more aggressive clinical features.Molecular analysis showed significant differences in molecular subtypes,TP53 mutation,ERBB2 amplification,ARID1A mutation,MSI status,and CpG island methylator phenotype category.Genomic analysis revealed that TP53 mutations,APC mutations,and ERBB2 amplifications were more frequent in GAPEP.Genes involved in methylation processes were highly upregulated in GAPEP.HAC and GAED shared similar clinicopathological and genetic characteristics.Functional enrichment analysis highlighted the critical role of methylation in the development of GAPEP.CONCLUSION The diversity and aggressiveness of GAPEP are driven by deregulated methylation,necessitating the integration of morphological and immunohistochemical diagnosis.Targeting methylation can provide new therapeutic opportunities for treating this aggressive cancer.
文摘BACKGROUND Mesonephric-like adenocarcinoma(MLA)is a rare and highly malignant disease that occurs in the uterine body or ovaries.We report a case of a MLA that was considered to have originated in the fallopian tube and presented with malignant peritonitis.CASE SUMMARY A 57-year-old female presented with a chief complaint of abdominal pain that began 2 months prior.Cancerous peritonitis was suspected.During exploratory laparoscopy,the right fallopian tube was found to be enlarged,with widespread disseminated lesions extending from the pelvic cavity to the upper abdomen.Histopathological examination of the peritoneal tissue obtained by biopsy showed tumor cells with a high nuclear/cellular ratio and proliferation of papillary tubular to pedunculated solid nests.Immunohistochemical testing was positive for GATA-binding protein 3,thyroid transcription factor 1,cluster of differentiation 10,and paired box protein-8,and negative for estrogen receptor,Wilms’tumor 1,and wild-type p53,leading to the diagnosis of MLA.Subsequently,debulking surgery was performed,and no macroscopic residual tumors were identified.The pathological diagnosis was right tubal carcinoma,mesonephric adenocarcinoma(International Federation of Gynecology and Obstetrics stage IIIC),and pT3cNXM0.Adjuvant chemotherapy was administered postoperatively;however,recurrence was noted,and the patient died 1 year and 6 months after the initial treatment.CONCLUSION MLA is a very rare disease with poor prognosis.Further studies are necessary to identify effective treatment options.
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.
文摘Background:To investigate SCL/TAL 1 interrupting locus(STIL)’s role and prognostic significance in lung adenocarcinoma(LUAD)progression,we examined STIL and E2 promoter binding factor 1(E2F1)expression and their impacts on LUAD prognosis using Gene Expression Profiling Interactive Analysis(GEPIA).Methods:Functional assays including CCK-8,wound-healing,5-ethynyl-2-deoxyuridine(EdU),Transwell assays,and flow cytometry,elucidated STIL and E2F1’s effects on cell viability,proliferation,apoptosis,and migration.Gene set enrichment analysis(GSEA)identified potential pathways,while metabolic assays assessed glucose metabolism.Results:Our findings reveal that STIL and E2F1 are overexpressed in LUAD,correlating with adverse outcomes.It enhances cell proliferation,migration,and invasion,and suppresses apoptosis,activating downstream of E2F1.Silencing E2F1 reversed the promotion effect of the STIL overexpression on cell viability and invasiveness.Importantly,STIL modulates glycolysis,influencing glucose consumption,lactate production,and energy balance in LUAD cells.Conclusion:Our model,incorporating STIL,age,and disease stage,robustly predicts patient prognosis,underscored STIL’s pivotal role in LUAD pathogenesis through metabolic reprogramming.This comprehensive approach not only confirms STIL’s prognostic value but also highlights its potential as a therapeutic target in LUAD.
基金supported by the National Natural Science Foundation of China(No.82272845)the Natural Science Foundation of Shandong(No.ZR2023ZD26).
文摘Objective:The neglect of occult lymph nodes metastasis(OLNM)is one of the pivotal causes of early non-small cell lung cancer(NSCLC)recurrence after local treatments such as stereotactic body radiotherapy(SBRT)or surgery.This study aimed to develop and validate a computed tomography(CT)-based radiomics and deep learning(DL)fusion model for predicting non-invasive OLNM.Methods:Patients with radiologically node-negative lung adenocarcinoma from two centers were retrospectively analyzed.We developed clinical,radiomics,and radiomics-clinical models using logistic regression.A DL model was established using a three-dimensional squeeze-and-excitation residual network-34(3D SE-ResNet34)and a fusion model was created by integrating seleted clinical,radiomics features and DL features.Model performance was assessed using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Five predictive models were compared;SHapley Additive exPlanations(SHAP)and Gradient-weighted Class Activation Mapping(Grad-CAM)were employed for visualization and interpretation.Results:Overall,358 patients were included:186 in the training cohort,48 in the internal validation cohort,and 124 in the external testing cohort.The DL fusion model incorporating 3D SE-Resnet34 achieved the highest AUC of 0.947 in the training dataset,with strong performance in internal and external cohorts(AUCs of 0.903 and 0.907,respectively),outperforming single-modal DL models,clinical models,radiomics models,and radiomicsclinical combined models(DeLong test:P<0.05).DCA confirmed its clinical utility,and calibration curves demonstrated excellent agreement between predicted and observed OLNM probabilities.Features interpretation highlighted the importance of textural characteristics and the surrounding tumor regions in stratifying OLNM risk.Conclusions:The DL fusion model reliably and accurately predicts OLNM in early-stage lung adenocarcinoma,offering a non-invasive tool to refine staging and guide personalized treatment decisions.These results may aid clinicians in optimizing surgical and radiotherapy strategies.
基金Supported by a grant from the National Natural Science Foundation of China(no.82174457)。
文摘Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung cancer potential.We aimed to explore the anti–lung cancer effect of BBR and related mechanisms by targeting the glycogen synthase kinase 3β(GSK3β)/β-catenin pathway.Methods:Lung adenocarcinoma(LUAD)cells A549 and NCI-H1975 were treated with BBR.Results:Our results showed that BBR inhibited cell proliferation by decreasing c-Myc levels and induced cel cycle arrest in the G0/G1 phase by lowering cyclin D1 levels.BBR induced apoptosis by upregulating cleaved caspase 3 levels.BBR inhibited cell migration and invasion by decreasing N-cadherin levels.Furthermore,BBR upregulated the expression of GSK3βprotein and phospho-β-catenin proteins in the cytoplasm,while decreasing the expression ofβ-catenin protein.Next,LUAD cel s were exposed to CHIR-99021(a GSK3βinhibitor).This treatment led to an increase in c-Myc,cyclin D1,andβ-catenin levels at specific concentrations.BBR partially reversed the effects of CHIR-99021.Finally,LUAD cells were treated with CHIR-99021(4μmoL/L)combined with BBR(30 and 60μmoL/L)for 24 h.The expression of programmed death ligand 1(PD-L1)was assessed by Western blot analysis.Jurkat T cells and A549 cel s were cocultured for 24 h to examine the lactate dehydrogenase release rate.Results suggested that BBR suppressed the expression of PD-L1 and heightened the immune lethality of T cells.Conclusions:BBR suppressed the proliferative activity of LUAD cell lines A549 and NCI-H1975 in vitro,induced cell cycle arrest and cancer cel apoptosis in the G0/G1 stage,and repressed the migration and invasion of cancer cells.BBR reduced the PD-L1 protein expression and enhanced T-cell–mediated cytotoxicity.These effects appear to be related to BBR's regulation of the GSK3β/β-catenin pathway.
基金supported by the 2022 Natural Science Foundation of Fujian Province(No.2022J011486).
文摘Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.
基金Supported by the Appropriate Technology Promotion Program in Chongqing,No.2023jstg005.
文摘BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram using internal and external validation to predict survival in patients with ampullary adenocarcinoma.METHODS Data were sourced from the surveillance,epidemiology,and end results stat database.The patients in the database were randomized in a 7:3 ratio into training and validation groups.Using Cox regression univariate and multivariate analyses in the training group,we identified independent risk factors for overall survival and cancer-specific survival to develop the nomogram.The nomogram was validated with a cohort of patients from the First Affiliated Hospital of the Army Medical University.RESULTS For overall and cancer-specific survival,12(sex,age,race,lymph node ratio,tumor size,chemotherapy,surgical modality,T stage,tumor differentiation,brain metastasis,lung metastasis,and extension)and 6(age;surveillance,epidemiology,and end results stage;lymph node ratio;chemotherapy;surgical modality;and tumor differentiation)independent risk factors,respectively,were incorporated into the nomogram.The area under the curve values at 1,3,and 5 years,respectively,were 0.807,0.842,and 0.826 for overall survival and 0.816,0.835,and 0.841 for cancer-specific survival.The internal and external validation cohorts indicated good consistency of the nomogram.CONCLUSION The dynamic nomogram offers robust predictive efficacy for the overall and cancer-specific survival of ampullary adenocarcinoma.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.
文摘The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp.39–45.
文摘In a recent study by He et al,the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen,thereby improving the accuracy of identifying high-risk patients compared to relying solely on preoperative markers,which has significant implications for customizing adjuvant therapy and potentially improving outcomes for this aggressive form of cancer.However,the study’s single-center design and short follow-up period may limit the generalizability of its findings and potentially introduce reporting bias.Future studies could consider additional confounding factors,such as adjuvant chemotherapy and variations in surgical techniques,to improve the model’s accuracy.Furthermore,it would be valuable to validate the nomogram in broader,prospective cohorts and explore the inclusion of additional markers like circulating tumor DNA to refine further its predictive power and applicability across diverse patient populations.
文摘BACKGROUND Ileum adenocarcinoma(IA),a type of small bowel adenocarcinoma,is a rather uncommon factor associated with obstruction in small bowel.Owing to its location and indefinite clinical symptoms,the diagnosis of IA is difficult,and survival is usually poor.With respect to the rarity of this disease,very few studies have reported such cases to provide a reference for treatment.CASE SUMMARY In this manuscript,a case of a 48-year-old man presented with chronic right lower abdominal pain and distention,queasiness and emesis.A computed tomography scan revealed intestinal wall thickening and an intestinal obstruction in the terminal ileum.He was diagnosed with inflammatory bowel disease.However,his symptoms were not relieved after conservative treatment.The patient sub-sequently underwent exploratory laparotomy,and a tumour in the ileum measuring approximately 2.0 cm×2.0 cm that was located 20 cm from the ileocolic valve was discovered incidentally and was operatively resected along with the enlarged lymph nodes.Pathological examination revealed a stage IIA(T3N0M0)ulcerative IA.Along with imaging examinations,a diagnosis of primary IA with no lymph or distant metastases was considered.The patient was discharged and recovered well as of the writing of this manuscript.CONCLUSION IA should be considered as a differential diagnosis in cases of intestinal obstruction,and the recommended method for local disease treatment is surgery.
基金funded by the Top Talent Support Program for Young and Middle-aged People of Wuxi Health Commission(No.BJ2023014)the General Program of Wuxi Medical Center of Nanjing Medical University(No.WMCG202406)the Quality Talent Program of Wuxi Medical Center of Nanjing Medical University(No.WMCQ202401)。
文摘Objective:A highly aggressive and lethal malignancy,characterized by its heterogeneity,lung adenocarcinoma(LUAD)presents significant challenges in prognosis and treatment.Disulfidptosis,a newly identified form of regulated cell death,offers novel insights into cancer progression,yet its role in LUAD remains poorly understood.Methods:We identified disulfidptosis-related genes(DRGs)from prior studies and analyzed their interactions and functional enrichment.Molecular subtypes were identified through consensus clustering based on DRG expression,and a prognostic DRG signature was developed using multivariate Cox regression analysis.A nomogram integrating clinical variables was developed to predict survival.Comprehensive analyses,including single-cell RNA sequencing,immune infiltration,and drug sensitivity,were validated using clinical specimens,LUAD cell lines,Western blotting(WB)and immunohistochemistry(IHC).Results:A total of 16 DRGs were identified,classifying LUAD patients into three distinct subtypes with differential survival and immune profiles.A 4-gene signature(GYS1,NDUFA11,NDUFB10,SLC7A11)was used to build a risk score model,demonstrating robust prognostic accuracy.A nomogram combining this signature with clinical features reliably predicted 1-,3-,and 5-year survival.The signature correlated with immune cell infiltration,with single-cell analysis revealing DRG enrichment in myeloid cells.Notably,SLC7A11 and GYS1 were positively associated with chemotherapeutic drug sensitivity.Validation through reverse transcription quantitative polymerase chain reaction(RT-qPCR),WB and IHC confirmed upregulated DRG expression in LUAD tissues and cell lines.Conclusions:This research highlights the essential role of DRGs in modulating the tumor microenvironment,influencing therapeutic response,and determining the prognosis of LUAD.The risk model and nomogram,derived from DRG expression,offer robust tools for survival prediction and personalized treatment stratification,facilitating the development of disulfidptosis-targeted therapeutic strategies.
基金funded by the Liaoning Province Science and Technology Plan Joint Project (No.2023JH2/101700140)
文摘Background:Lung adenocarcinoma,the most prevalent lung cancer subtype,is increasingly diagnosed in non-smokers and females.The cell cycle regulator CDC20(Cell Division Cycle 20),a crucial activator of the Anaphase-Promoting Complex/Cyclosome(APC/C),is frequently overexpressed in various cancers,including lung adenocarcinoma,and is implicated in tumorigenesis.Preclinical studies indicate that inhibiting the CDC20-APC/C signaling axis can enhance chemotherapy-induced apoptosis.Analysis of The Cancer Genome Atlas(TCGA)data confirms that elevated CDC20 expression in lung adenocarcinoma is significantly associated with poorer patient prognosis and correlates with immune cell infiltration.These collective findings highlight CDC20 as a promising prognostic biomarker and a potential novel therapeutic target for lung adenocarcinoma.Methods:We collected 539 patients with LUAD and 59 normal controls of clinical data from the Cancer Genome Atlas(TCGA)for bioinformatics analysis to investigate the role of CDC20 in LUAD and address the above questions.We evaluated the association between CDC20 expression and clinicopathological features using the Kruskal Wallis test and multivariate logistic regression.Prognostic values were assessed using Cox regression and Kaplan-Meier survival analyses.We further used single-sample gene set enrichment analysis(ssGSEA)to explore correlations between CDC20 expression and immune infiltration levels.Results:CDC20 expression in LUAD tissues was significantly higher than that in normal controls(p<0.001)and showed high diagnostic accuracy(AUC[area under the curve]=0.979).Kaplan-Meier analysis revealed that high CDC20 expression predicted poorer overall survival(OS;HR=1.47,95%CI:1.10–1.97,p=0.009),although no significant association emerged with progression-free interval(p=0.172).ssGSEA indicated a strong positive correlation between CDC20 and T helper 2 cell infiltration(R=0.764,p<0.001),but negative correlations with mast cells(R=−0.469,p<0.001)and eosinophils(R=−0.343,p<0.001).Functional enrichment analyses(Gene ontology/Kyoto Encyclopedia of Genes and Genomes[GO/KEGG])of CDC20-associated genes provided additional mechanistic insights.Conclusions:The significantly elevated expression of CDC20 in LUAD tissues,coupled with its high diagnostic accuracy(AUC=0.979),underscores its potential utility in differentiating LUAD from normal tissue.More importantly,the strong association between high CDC20 expression and poorer overall survival(OS)establishes its independent prognostic value for predicting adverse patient outcomes.Beyond its correlation with clinical parameters,our findings illuminate potential mechanisms underlying CDC20's oncogenic role.The distinct positive correlation with T helper 2(Th2)cell infiltration and negative correlations with mast cells and eosinophils suggest that CDC20 may actively shape an immunosuppressive tumor microenvironment,potentially facilitating tumor immune evasion and progression.Functional enrichment analyses of CDC20-coexpressed genes further support its involvement in key oncogenic pathways,including cell cycle regulation and mitotic processes.Collectively,this study not only validates CDC20 as a valuable prognostic factor but also provides novel mechanistic insights linking its overexpression to altered immune landscapes in LUAD.
基金supported by the National Natural Science Foundation of China(82002432 to J.W.,82302068 to M.Z.,and 32300568 to T.W.)the Natural Science Foundation of Shandong Province(ZR2024MH159 to Y.Z.,ZR2020QH179 to J.W.,ZR2022QH057 to M.Z.,and ZR2021QH005 to T.W.)the China Postdoctoral Science Foundation(2024M752006 to S.M.)。
文摘Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma(LUAD)have been identified,the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear.Using spatial transcriptomics and single-cell RNA-sequencing data from multi-regional LUAD biopsies consisting of tumor core,tumor edge,and normal area,we sought to delineate the spatial heterogeneity and driving factors of cell colocalization.Two cancer cell sub-clusters(Cancer_c1 and Cancer_c2),associated with LUAD initiation and metastasis,respectively,exhibit distinct spatial distributions and immune cell colocalizations.In particular,Cancer_c1,enriched within the tumor core,could directly interact with B cells or indirectly recruit B cells through macrophages.Conversely,Cancer_c2 enriched within the tumor edge exhibits colocalization with CD8^(+)T cells.Collectively,our work elucidates the spatial distribution of cancer cell subtypes and their interaction with immune cells in the core and edge of LUAD,providing insights for developing therapeutic strategies for cancer intervention.
基金Key Research and Development Foundation supported by Science and Technology Department of Sichuan Province.Project Number:2023YFS0243Project Name:Application of Multiple Nucleic Acid Detection of Respiratory Pathogens Based on Multiple Fusion Curve Technology in Rapid Pathogenic Analysis of Acute Respiratory Distress Syndrome Patients Caused By Atypical Pathogen Infections in Emergency Departments+1 种基金Fund Name:Applied Basic Research Foundation supported by Science and Technology Department of Sichuan Province.Project Number:2021YJ0135Project Name:Explorating the Antiinflammatory Mechanism of Extracellular Vesicles Secreted by Wharton’s Jelly Mesenchymal Stem Cells in Alleviating Pulmonary Vascular Endothelial Injury and Discussing the Effectiveness of VEGF Gene Modification in Sepsis-related ALI/ARDS.
文摘Background:The centrosome,a crucial cellular structure involved in the mitotic process of eukaryotic cells,plays a significant role in tumor progression by regulating the growth and differentiation of neoplastic cells.This makes the centrosome a promising target for therapeutic strategies in cancer treatment.Methods:Utilizing data from the TCGA database,we identified centrosome-related genes and constructed a prognostic model for 518 lung adenocarcinoma patients.Prognosis-associated genes were initially screened using univariate Cox regression,with overfitting minimized by applying LASSO regression to remove collinearity.Finally,a set of 12 genes was selected through multivariable Cox regression for inclusion in the prognostic model.Results:The model’s performance was assessed using ROC curve analysis,demonstrating a robust predictive ability with an AUC of 0.728 in the training group and 0.695 in the validation group.Differential expression analysis between high-risk(HRLAs)and low-risk(LRLAs)individuals was performed,followed by enrichment analyses using KEGG,GO,Progeny,GSVA,and GSEA.These analyses revealed significant differences in immune-related pathways between the two groups.Immune microenvironment assessment through ssGSEA and ESTIMATE indicated that individuals with poor prognosis exhibited lower immune,stromal,and ESTIMATE scores,along with higher tumor purity,suggesting an impaired immune microenvironment in HRLAs patients.Drug susceptibility analysis and molecular docking showed that HRLAs individuals were more responsive to docetaxel,emphasizing the therapeutic relevance of paclitaxel in this cohort.Conclusion:We successfully developed and validated a centrosome-associated gene-based prognostic model,offering clinicians valuable insights for improved decision-making and personalized treatment strategies.This model may facilitate the identification of high-risk patients and guide therapeutic interventions in lung adenocarcinoma.
基金supported by the National Key Research and Development Program of China(Grant No.2021YFA1201100)the Projects of Tianjin Science and Technology Bureau National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine(Grant Nos.24ZXZSSS00440 and 22ZXJBSY00030)+1 种基金the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2022ZD067)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Objective:The aim of the current study was to identify independent prognostic factors,evaluate differential adjuvant chemotherapy efficacy across clinicopathologic subgroups,and define adjuvant chemotherapy-sensitive populations.Methods:A retrospective analysis of 168 AAC patients undergoing curative pancreaticoduodenectomy(2011-2020)was performed.Cases were classified into intestinal(28.0%),pancreatobiliary(30.4%),and mixed subtypes(18.5%)per NCCN(v2.2025)criteria.Independent prognostic factors for AAC patients were identified through uni-and multi-variable Cox proportional hazards modeling and subgroup analyses were stratified by age range,gender,differentiation,T stage,N stage,BVI,TDs,and PNI.Results:The pancreatobiliary signature(HR=2.884,P<0.001)and BVI(HR=2.330,P=0.001)were independent poor prognostic factors.Adjuvant chemotherapy improved overall survival(OS)in the following AAC patients:T3-T4 stage(HR=0.485,P=0.050);N1-N2 stage(HR=0.365,P=0.008);and TD-positive(HR=0.401,P=0.026).The median OS increased from 22.3-51.3 months with adjuvant chemotherapy in TD-positive patients(P=0.019).TD positivity conferred a worse prognosis in BVI-negative subgroups(OS:HR=3.840,95%CI:2.058-7.166,P<0.001;and progression-free survival(PFS):HR=2.950,95%CI:1.550-5.617,P=0.002).Conclusions:The pancreatobiliary signature and BVI constitute critical high-risk pathologic features in AAC.TD status identified high-risk cohorts,thus enabling postoperative risk-stratified treatment strategies.In patients negative for pancreatobiliary signature or BVI,TD positivity predicted significantly worse survival.
基金supported by the Natural Science Foundation of Shandong Province(ZR2021MH110,ZR2020MH257,ZR2020MH323)the National Natural Science Foundation of China(82172339 and 82272410)+1 种基金Major Scientific and Technological Innovation Project of Shandong Province(2021CXGC010603 and 2021CXGC011105)Taishan Scholar Program of Shandong Province(tstp20221156 and tsqn202306346).
文摘Lysosomal dysfunction has been implicated in the progression of colon adenocarcinoma(COAD),yet the prognostic significance and therapeutic potential of lysosome-related genes(LRGs)remain underexplored.In this study,we construct a 6-LRG-based prognostic risk stratification model(DPP7,ADAM8,CD1B,LRP2,ATP6V1C2,and PLAAT3)by integrating LASSO and Cox regression analyses.Stratifying patients based on median risk scores,we demonstrate that high-risk patients exhibit significantly worse clinical outcomes across the TCGA cohort and five independent GEO datasets.Furthermore,this panel outperforms 136 previously published models in terms of predictive accuracy for 1-,3-,and 5-year survival rates.Validation multiplex immunofluorescence using an in-house tissue microarray cohort confirms that the 6-LRG signature serves as an independent prognostic factor.Additionally,high-risk patients exhibit distinct immunosuppressive tumor microenvironment and aggressive malignancy characteristics.Functional depletion of DPP7 significantly inhibits tumor cell proliferation,migration,and metastasis in both in vitro and in vivo settings.Moreover,DPP7 silencing attenuates epithelialemesenchymal transition,as evidenced by the upregulation of E-cadherin and downregulation of N-cadherin,Vimentin,and Snail.In conclusion,this study establishes an LRG-based model for COAD prognostic prediction and nominates DPP7 as a promising therapeutic target for COAD treatment.
基金Supported by Guangxi Guilin Science and Technology Fund,No.20190218-7-6.
文摘BACKGROUND Most non-small cell lung cancer patients have epidermal growth factor receptor(EGFR)activating mutations,such as exon 19 deletion and exon 21 replacement mutations.Osimertinib is a third-generation EGFR-tyrosine kinase inhibitors ap-proved for the treatment of lung cancer patients carrying EGFR activating mu-tations.Osimertinib-induced interstitial lung disease(ILD)is a rare and poten-tially fatal pulmonary toxic manifestation of drug therapy.At present,there is no international consensus on the risks and treatment of the osimertinib-induced ILD.CASE SUMMARY We report a case of a 56-year-old woman who was diagnosed with lung adenocar-cinoma with lung hilum,mediastinal lymph nodes and brain metastases(T4N3-M1c stage IVB).The patient received targeted treatment with osimertinib after radiotherapy and chemotherapy.But she developed ILD after osimertinib treat-ment.Following active symptomatic treatment and hormone treatment,the lung injury alleviated.The patient was retreated with furmonertinib combined with prednisone and did not experience ILD again.So far,she has survived for 14 months without disease progression.CONCLUSION Retreatment with furmonertinib under prednisone could be considered as an effective therapeutic option after risk-benefit assessment for EGFR-mutant lung adenocarcinoma patients.
