This study aims to explore the expression of stanniocalcin 2(STC2)gene in breast cancer and its clinical significance.Female patients with breast cancer from Zhongnan Hospital of Wuhan University admitted during March...This study aims to explore the expression of stanniocalcin 2(STC2)gene in breast cancer and its clinical significance.Female patients with breast cancer from Zhongnan Hospital of Wuhan University admitted during March 2014 to October 2014 were enrolled in this study.All the tissues used in this experiment included 50 cases of breast cancer tissues and corresponding 50 cases of paracancer normal breast tissues with complete patients'information.The real-time quantitative polymerase chain reaction(qPCR)was applied to detect the expression of STC2 gene in 50 cases of breast cancer and paracancer normal breast tissues.The results showed that the expression level of STC2 gene in 50 cases of breast cancer tissues was significantly higher than that in paracancer normal breast tissues(P<0.001).The expression of STC2 gene was correlated with lymph node metastasis,distant metastasis,TNM stage and histological grade(P<0.001).The expression level of STC2 gene was significantly higher in breast cancer tissues with higher expression of Ki-67(P<0.001).The expression level of STC2 gene was significantly higher in estrogen receptor(ER)positive breast cancer tissues than in ER negative ones(P<0.001).However,different groups of age,pathological type,tumor size,PR expression and human epidermal growth factor receptor-2(HER2)expression did not show significant differences in STC2 expression(P>0.05).In conclusion,the abnormal overexpression of STC2 gene may play a role in the development and progression of breast cancer,and it can be used as an independent metastasis and prognostic factor of breast cancer.In addition,STC2 gene probably promotes the development and metastasis of breast cancer by interacting with estrogen and ER,and it may become a new direction for breast cancer endocrine therapy.展开更多
Colorectal cancer(CRC)is a type of cancer that grows from polypoid lesions developing over the years.It has a high incidence of about 1.8 million new cases annually.While screening and lifestyle modifications have sta...Colorectal cancer(CRC)is a type of cancer that grows from polypoid lesions developing over the years.It has a high incidence of about 1.8 million new cases annually.While screening and lifestyle modifications have stabilized the rate of CRC in high-income countries,the incidence of early-onset CRC is increasing globally.The worst prognosis for this cancer is linked to recurrence and metastasis,with peritoneal metastasis occurring in 8%to 20%of cases.In these cases,treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is indicated.However,this approach is risky and requires careful selection of patients who will truly benefit from it.This article will discuss the correlation between nutrition and inflammation in patients with peritoneal metastasis and advanced CRC,emphasizing the importance of nutritional and inflammatory markers for assessing disease status.Finally,we will highlight the main biomarkers in the field.展开更多
As one of the most prevalent malignant tumors,hepatocellular carcinoma(HCC)represents a major global public health burden.Traditionally,HCC pathogenesis has been attributed to chronic liver diseases(viral hepatitis,ci...As one of the most prevalent malignant tumors,hepatocellular carcinoma(HCC)represents a major global public health burden.Traditionally,HCC pathogenesis has been attributed to chronic liver diseases(viral hepatitis,cirrhosis)and aflatoxin exposure.However,with evolving lifestyles and environmental changes,sleep disorders have become increasingly prevalent.Emerging evidence suggest that sleep disorders may contribute to hepatocarcinogenesis through multiple mechanisms,including immunity environment disorder,oxidative stress,metabolic dysregulation,disruption of gut microbiota,and circadian rhythm disruption,thereby influencing disease progression and patient prognosis.This review summarizes epidemiological evidence on the relationship between sleep disorders and HCC incidence,explores the underlying mechanisms through which sleep disorders contribute to HCC,and discusses clinical challenges and potential intervention strategies.Our objective is to provide novel insights into HCC prevention and therapeutic approaches.展开更多
AIM To evaluate recent trends in gastric cancer incidence, response to treatment, and overall survival among Alaska Native(AN) people. METHODS A retrospective analysis of the Alaska Native Medical Center patient datab...AIM To evaluate recent trends in gastric cancer incidence, response to treatment, and overall survival among Alaska Native(AN) people. METHODS A retrospective analysis of the Alaska Native Medical Center patient database was performed. Patient history, clinical, pathological, response to treatment and patient outcomes were collected from one-hundred and thirty-two AN gastric cancer patients. The Surveillance, Epidemiology and End Result database 18 was used to collect comparison United States non-Hispanic White(NHW) and AN gastric cancer patient data between 2006-2014.RESULTS AN gastric cancer patients have a higher incidence rate, a poorer overall survival, and are diagnosed at a significantly younger age compared to NHW patients. AN patients differ from NHW patients in greater prevalence of non-cardia, diffuse subtype, and signet ring cell carcinomas. AN females were more likely to be diagnosed with later stage cancer, stage IV, compared to AN males. Diminished overall survival was observed among AN patients with increasing stage, O+ blood type, < 15 lymph nodes examined at resection, and no treatment. This study is the first report detailing the clinicopathologic features of gastric cancer in AN people with outcome data.CONCLUSION Our findings confirm the importance of early detection, treatment, and surgical resection for optimizing AN patient outcomes. Further research on early detection markers are warranted.展开更多
Pancreatic ductal adenocarcinoma(PDA)is among the deadliest cancers in the United States and in the world.Late diagnosis,early metastasis and lack of effective therapy are among the reasons why only 6%of patients diag...Pancreatic ductal adenocarcinoma(PDA)is among the deadliest cancers in the United States and in the world.Late diagnosis,early metastasis and lack of effective therapy are among the reasons why only 6%of patients diagnosed with PDA survive past 5 years.Despite development of targeted therapy against other cancers,little progression has been made in the treatment of PDA.Therefore,there is an urgent need for the development of new treatments.However,in order to proceed with treatments,the complicated biology of PDA needs to be understood first.Interestingly,majority of the tumor volume is not made of malignant epithelial cells but of stroma.In recent years,it has become evident that there is an important interaction between the stromal compartment and the less prevalent malignant cells,leading to cancer progression.The stroma not only serves as a growth promoting source of signals but it is also a physical barrier to drug delivery.Understanding the tumor-stroma signaling leading to development of desmoplastic reaction and tumor progression can lead to the development of therapies to decrease stromal activity and improve drug delivery.In this review,we focus on how the current understanding of biology of the pancreatic tumor microenvironment can be translated into the development of targeted therapy.展开更多
Prostate cancer(PCa)is the most commonly diagnosed cancer among men in western countries.Androgen receptor(AR)signaling plays key roles in the development of PCa.Androgen deprivation therapy(ADT)remains the standard t...Prostate cancer(PCa)is the most commonly diagnosed cancer among men in western countries.Androgen receptor(AR)signaling plays key roles in the development of PCa.Androgen deprivation therapy(ADT)remains the standard therapy for advanced PCa.In addition to its ligand androgen,accumulating evidence indicates that posttranscriptional modification is another important mechanism to regulate AR activities during the progression of PCa,especially in castration resistant prostate cancer(CRPC).To date,a number of posttranscriptional modifications of AR have been identified,including phosphorylation(e.g.by CDK1),acetylation(e.g.by p300 and recognized by BRD4),methylation(e.g.by EZH2),ubiquitination(e.g.by SPOP),and SUMOylation(e.g.by PIAS1).These modifications are essential for the maintenance of protein stability,nuclear localization and transcriptional activity of AR.This review summarizes posttranslational modifications that influence androgen-dependent and-independent activities of AR,PCa progression and therapy resistance.We further emphasize that in addition to androgen,posttranslational modification is another important way to regulate AR activity,suggesting that targeting AR posttranslational modifications,such as proteolysis targeting chimeras(PROTACs)of AR,represents a potential and promising alternate for effective treatment of CRPC.Potential areas to be investigated in the future in the field of AR posttranslational modifications are also discussed.展开更多
AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected...AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected in 527 individuals, including 115 healthy control(HC), 198 colorectal adenoma(CA), and 214 CC individuals in the training group. RESULTS Serum TFF3 showed no significant correlation with age, gender, or tumor location but showed significant correlation with the tumor stage. Serum TFF3 in the CC group was significantly higher than in the HC or CA group. The AUC values of TFF3 for discriminating between HC and CC and between CA and CC were 0.930(0.903, 0.958) and 0.834(0.796, 0.873). A multivariate model combining TFF3 and CEA was built. Compared to TFF3 or CEA alone, the multivariate model showed significant improvement(P < 0.001). For discriminating between HC and CC, HC and early stage CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%, 93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%, 93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%, respectively. CONCLUSION The multivariate diagnostic model that included TFF3 and CEA showed significant improvement over the conventional biomarker CEA and might provide a potential method for the early detection of CC.展开更多
Objective Gastric cancer(GC)is a deadly cancer and a challenging public health problem globally.This study aimed to analyze potential genes associated with pathogenesis and prognosis of gastric cancer.Methods This wor...Objective Gastric cancer(GC)is a deadly cancer and a challenging public health problem globally.This study aimed to analyze potential genes associated with pathogenesis and prognosis of gastric cancer.Methods This work selected the overlapping differentially expressed genes(DEGs)in GC from four datasets,the GSE29272,GSE29998,GSE54129 and GSE118916 Gene Expression Omnibus databases.These DEGs were used to carry out comprehensive bioinformatic analysis to analyze the related functions and pathways enriched,the relative expression levels and immune infiltrates,the prognostic characteristics and the interaction network.Results In total,55 DEGs increased while 98 decreased in their expression levels.For those DEGs with increased expression,they were mostly concentrated on“focal adhesion”and“ECM-receptor interaction”,whereas DEGs with decreased expression were mostly associated with“gastric acid secretion”and“drug metabolism cytochrome P450”.MCODE and ClueGO results were then integrated to screen 10 hub genes,which were FN1,COL1A1,COL3A1,BGN,TIMP1,COL1A2,LUM,VCAN,COL5A2 and SPP1.Survival analysis revealed that higher expression of the ten hub genes significantly predicted lower overall survival of GC patients.TIMP1 was most significantly related to neutrophils,CD8+T cells,as well as dendritic cells,while LUM was most significantly related to macrophages.Conclusion Immunohistochemistry results and functional testing showed that the expression of COL5A2 was elevated in GC and that it might be a key gene in GC tumorigenesis.展开更多
BACKGROUND Gemcitabine plus platinum is the standard of care first-line treatment for advanced biliary tract cancers(BTC).There is no established second-line therapy,and retrospective reviews report median progression...BACKGROUND Gemcitabine plus platinum is the standard of care first-line treatment for advanced biliary tract cancers(BTC).There is no established second-line therapy,and retrospective reviews report median progression-free survival(PFS)less than 3 mo on second-line therapy.5-Fluorouracil plus irinotecan(FOLFIRI)is a commonly used regimen in patients with BTC who have progressed on gemcitabine plus platinum,though there is a paucity of data regarding its efficacy in this population.AIM To assess the efficacy of FOLFIRI in patients with biliary tract cancers.METHODS We retrospectively identified patients with advanced BTC who were treated with FOLFIRI at MD Anderson,University of Michigan and Mayo Clinic in Jacksonville.Data were collected on patient demographics,BTC subtype,response per RECIST v1.1,progression and survival.RESULTS Ninety-eight patients were included of which 74(75%)had metastatic and 24(25%)had locally advanced disease at the time of treatment with FOLFIRI.The median age was 60(range,22-86)years.The number of patients with extrahepatic cholangiocarcinoma,gall bladder cancer and intrahepatic cholangiocarcinoma were 10,17 and 71,respectively.FOLFIRI was used as 1st,2nd,3rd or 4th–Nth lines in 8,50,36 and 4 patients,respectively.Median duration on FOLFIRI in the entire cohort was 2.2(range,0.5-8.4)mo.The median PFS and overall survival were 2.4(95%confidence interval(CI):1.7-3.1)and 6.6(95%CI:4.7-8.4)mo,respectively.Median PFS for patients treated with FOLFIRI in 1st,2nd,3rd or 4th–Nth lines were 3.1,2.5,2.3 and 1.5 mo,respectively.Eighteen patients received concurrent bevacizumab(n=13)or EGFR-targeted therapy(n=5)with FOLFIRI,with a median PFS of 2.7 mo(95%CI:1.7-5.1).CONCLUSION In this largest multi-institution retrospective review of 98 patients with BTC treated with FOLFIRI,efficacy appears to be modest with outcomes similar to other cytotoxic chemotherapy regimens.展开更多
Recent studies showed that inflammation is a critical cause for initiation and/or development of many cancers. In prostate cancer(PC), the inflammatory cells usually populate an immune-competent organ. This inflammato...Recent studies showed that inflammation is a critical cause for initiation and/or development of many cancers. In prostate cancer(PC), the inflammatory cells usually populate an immune-competent organ. This inflammatory organ can be involved in the initiation and progression of PC. Here, we mainly focus on the role of inflammation in the PC and progression of castration-resistant PC(CRPC). Moreover, we summarize the roles of inflammation factors(such as chemokines and cytokines) in PC and CRPC. Taken together, this review gives an insight into therapy for PC and CRPC through anti-inflammation.展开更多
Objective:The eukaryotic release factor 3a(eRF3a),a member of the eukaryotic peptide chain release factor family,is overexpressed in several types of cancer.This study aims to investigate the biological role and mecha...Objective:The eukaryotic release factor 3a(eRF3a),a member of the eukaryotic peptide chain release factor family,is overexpressed in several types of cancer.This study aims to investigate the biological role and mechanism of eRF3a in the progression of liver cancer.展开更多
Objective:The present study was aimed to identify novel key genes,prognostic biomarkers and molecular pathways implicated in tumorigenesis of colon cancer.Methods:The microarray data GSE41328 containing 10 colon cance...Objective:The present study was aimed to identify novel key genes,prognostic biomarkers and molecular pathways implicated in tumorigenesis of colon cancer.Methods:The microarray data GSE41328 containing 10 colon cancer samples and 10 adjacent normal tissues was analyzed to identify 4763 differentially expressed genes.Meanwhile,another microarray data GSE17536 was performed for weighted gene co-expression network analysis(WGCNA).Results:In present study,12 co-expressed gene modules associated with tumor progression were identified for further studies.The red module showed the highest association with pathological stage by Pearson's correlation analysis.Functional enrichment analysis revealed that genes in red module focused on cell division,cell proliferation,cell cycle and metabolic related pathway.Then,a total of 26 key hub genes were identified,and GEPIA database was subsequently selected for validation.Holliday junction-recognizing protein(HJURP)and cell division cycle 25 homolog C(CDC25C)were identified as effective prognosis biomarkers,which were all detrimental to prognosis.Gene set enrichment analyses(GSEA)found the two hub genes were enriched in“oocyte meiosis”,“oocyte maturation that are progesterone-mediated”,“p53 signaling pathway”,and“cell cycle”.Furthermore,the immunohistochemistry and western blotting showed that HJURP was highly expressed in colon cancer tissue.Conclusion:HJURP was identified as a key gene associated with colon cancer progression and prognosis by WGCNA,which might influence the prognosis by regulating cell cycle pathways.展开更多
Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cell...Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.展开更多
The androgen receptor （AR） is a pleio-trophic transcription factor that regu-lates expression of a large number of genes involved in many diverse cellular processes. The AR activation pathways have been studied exte...The androgen receptor （AR） is a pleio-trophic transcription factor that regu-lates expression of a large number of genes involved in many diverse cellular processes. The AR activation pathways have been studied extensively. However, the molecular mechanism and biological significance of AR inhibitory signals remain poorly understoo＆ Mukhopadhyay et aL have now identified the nuclear matrix protein scaffold attachmenl factor B1 （SAFB1） as a novel AR corepressor. The authors found that SAFB1 physically associates with AR protein and inhibits AR transcriptional activity and androgen-sens- itive gene expression. SAFB1 had no effect on chromatin occupancy of AR, but silencin of SAFB1 abolished recruitment MST1, known AR repressor, at AR target loci. The also showed that SAFB1 interacts with EZH2 SUZ12 and EED, three core components o the Polycomb repressive complex 2 （PRC2）, which catalyzes the gene repression histone modification H3 lysine 27 trimethylation （H3K27me3）. The authors further showed that forced expression of SAFB1 increases H3K27me3 at AR target loci and this effec requires EZH2. Finally, the authors demon strated that expression of SAFB1 is downre-guiated in human prostate cancer （PCa） specimens and SAFB1 knockdown results in an aggressive phenotype of PCa. These find-ings identify SAFB1 as an important node for integration of multiple inhibitory signals ot AR, which represents a viable pathway fol therapeutic intervention of PCa.展开更多
In sub-Saharan Africa, breast cancer (BC) constitutes a serious public health problem and the genetic basis of its development is remaining poorly understood. Although the SNPs at codon 72 of <em>TP</em>53...In sub-Saharan Africa, breast cancer (BC) constitutes a serious public health problem and the genetic basis of its development is remaining poorly understood. Although the SNPs at codon 72 of <em>TP</em>53 (rs1042522) and at the UTR of <em>SET</em>8 (rs16917496) have both been associated with BC development among Asian and European women, no published data has been reported within African population. We herein report on the impact of these polymorphisms on the risk of BC among Cameroonian women. Blood samples were collected from 111 breast cancer patients and 224 controls. DNA was extracted from each sample and PCR-RFLP was used to investigate the polymorphisms at SNPs rs1042522 of <em>TP</em>53 and rs16917496 of <em>SET</em>8. Association studies were performed according to ethno-linguistic groups and menopausal status. The minor allele “T” of <em>SET</em>8 gene revealed a protective effect in premenopausal women (OR, 0.327;95% CI 0.125 - 0.852) while the CT genotype of <em>SET</em>8 was associated with increased risk of BC (OR, 2.93;95% CI, 1.1 - 7.8). The minor “G” allele of <em>TP</em>53 gene was significantly associated (OR, 2.533;95% CI, 1.455 - 4.408) with increased disease risk in premenopausal women while the CG genotype was significantly associated (OR, 0.39;95% CI, 0.23 - 0.69) with decreased risk of BC. A synergistic genetic interaction at both loci for CC genotype of SET8 and CG genotype of <em>TP</em>53 was associated (OR, 0.46;95% CI, 0.24 - 0.91) with reduced disease risk. No significant association between polymorphisms at the SET8 and <em>TP</em>53 loci and clinical pathologic features of BC was observed. This study suggests significant associations between the SNPs located at the 3’-UTR of <em>SET</em>8 and codon 72 of the <em>TP</em>53 with the risk of breast cancer development among premenopausal women. There is an interaction between <em>TP</em>53 and <em>SET</em>8 genes.展开更多
Background:Elevated levels of circulating endothelial cells might reflect significant vascular damage and dysfunction.Recent studies have shown that circulating endothelial cells levels are related to therapeutic resp...Background:Elevated levels of circulating endothelial cells might reflect significant vascular damage and dysfunction.Recent studies have shown that circulating endothelial cells levels are related to therapeutic responses of tumors,and thus,could be used as an indicator to predict the efficacy of tumor treatments.The purpose of this study was to investigate the correlation and impact of endothelial cells with and on the efficacy of first-line therapy(platinum-based or tyrosine kinase inhibitor drugs treatments)for advanced non-small-cell lung cancer.Methods:We analyzed 45 inpatients who met the inclusion criteria of diagnosis with inoperable non-small-cell lung cancer stages III and IV,in the People’s Hospital of Guangxi Zhuang Autonomous Region from January 2019 to January 2020.The flow cytometry technique was adopted to detect pretreatment levels of circulating endothelial cells in peripheral blood of patients with advanced non-small-cell lung cancer.The pretreatment peripheral blood was collected to analyze the relations of circulating endothelial cells with different clinical characteristics and efficacy.Results:The level of pretreatment circulating endothelial cells was significantly correlated with the efficacy of treatment(P<0.05)but irrelevant to the patient’s physical conditions,pathological type,tumor stage,and pretreatment serum carcinoembryonic antigen(P>0.05).The comparison between the groups of response(complete response+partial response)and nonresponse(stable disease+progressive disease)showed a significant difference in circulating endothelial cells count.Compared with low levels of circulating endothelial cells,a high level of circulating endothelial cells led to a poor efficacy(P<0.05).Conclusion:The level of pretreatment circulating endothelial cells significantly correlated with the efficiency of first-line therapy for non-small-cell lung cancer.Compared with low level of circulating endothelial cells,high level of circulating endothelial cells lead to poor efficacy.Therefore,circulating endothelial cell is indeed an effective indicator for predicting the efficacy of first-line therapy for advanced non-small-cell lung cancer.展开更多
Newer systemic therapies for hepatocellular carcinoma(HCC)have led to growing interest in combining hepatic arterial infusion chemotherapy(HAIC)with systemic treatments.To evaluate the effectiveness and safety of HAIC...Newer systemic therapies for hepatocellular carcinoma(HCC)have led to growing interest in combining hepatic arterial infusion chemotherapy(HAIC)with systemic treatments.To evaluate the effectiveness and safety of HAIC and combination therapies in treating advanced HCC,a network meta-analysis was conducted by Zhou et al.The study included data from 44 articles.HAIC was superior in overall survival(OS),progression-free survival(PFS),and response rates compared to transarterial chemoembolization and sorafenib.Moreover,combinations of HAIC with other treatments and single agents(e.g.,lenvatinib,ablation,anti-programmed cell death 1 therapy,radiotherapy)provided better OS and PFS outcomes than HAIC alone.In this editorial,we will discuss the study findings,the strengths and weaknesses of the metanalysis,and future advances in the field of HAIC for advanced HCC.展开更多
Accurate prognosis prediction is essential for guiding cancer treatment and improving patient outcomes.While recent studies have demonstrated the potential of histopathological images in survival analysis,existing mod...Accurate prognosis prediction is essential for guiding cancer treatment and improving patient outcomes.While recent studies have demonstrated the potential of histopathological images in survival analysis,existing models are typically developed in a cancerspecific manner,lack extensive external validation,and often rely on molecular data that are not routinely available in clinical practice.To address these limitations,we present PROGPATH,a unified model capable of integrating histopathological image features with routinely collected clinical variables to achieve pancancer prognosis prediction.PROGPATH employs a weakly supervised deep learning architecture built upon the foundation model for image encoding.Morphological features are aggregated through an attention-guided multiple instance learning module and fused with clinical information via a cross-attention transformer.A router-based classification strategy further refines the prediction performance.PROGPATH was trained on 7999 whole-slide images(WSIs)from 6,670 patients across 15 cancer types,and extensively validated on 17 external cohorts with a total of 7374 WSIs from 4441 patients,covering 12 cancer types from 8 consortia and institutions across three continents.PROGPATH achieved consistently superior performance compared with state-of-the-art multimodal prognosis prediction models.It demonstrated strong generalizability across cancer types and robustness in stratified subgroups,including early-and advancedstage patients,treatment cohorts(radiotherapy and pharmaceutical therapy),and biomarker-defined subsets.We further provide model interpretability by identifying pathological patterns critical to PROGPATH’s risk predictions,such as the degree of cell differentiation and extent of necrosis.Together,these results highlight the potential of PROGPATH to support pancancer outcome prediction and inform personalized cancer management strategies.展开更多
基金grants from National Natural Science Foundation of China(No.81072152 and No.81770283)Natural Science Foundation of Hubei Province(No.2015CFA027)+3 种基金Research Foundation of Health and Family Planning Commission of Hubei Province(No.WJ2015MA010 and No.WJ2017M249)Clinical Medical Research Center of Peritoneal Cancer of Wuhan(No.2015060911020462)Subsidy Project of No.1 Hospital of Lanzhou University(No.Idyyyn2018-13)Research Foundation of Health and Family Planning Commission of Changzhou(No.QN201824).
文摘This study aims to explore the expression of stanniocalcin 2(STC2)gene in breast cancer and its clinical significance.Female patients with breast cancer from Zhongnan Hospital of Wuhan University admitted during March 2014 to October 2014 were enrolled in this study.All the tissues used in this experiment included 50 cases of breast cancer tissues and corresponding 50 cases of paracancer normal breast tissues with complete patients'information.The real-time quantitative polymerase chain reaction(qPCR)was applied to detect the expression of STC2 gene in 50 cases of breast cancer and paracancer normal breast tissues.The results showed that the expression level of STC2 gene in 50 cases of breast cancer tissues was significantly higher than that in paracancer normal breast tissues(P<0.001).The expression of STC2 gene was correlated with lymph node metastasis,distant metastasis,TNM stage and histological grade(P<0.001).The expression level of STC2 gene was significantly higher in breast cancer tissues with higher expression of Ki-67(P<0.001).The expression level of STC2 gene was significantly higher in estrogen receptor(ER)positive breast cancer tissues than in ER negative ones(P<0.001).However,different groups of age,pathological type,tumor size,PR expression and human epidermal growth factor receptor-2(HER2)expression did not show significant differences in STC2 expression(P>0.05).In conclusion,the abnormal overexpression of STC2 gene may play a role in the development and progression of breast cancer,and it can be used as an independent metastasis and prognostic factor of breast cancer.In addition,STC2 gene probably promotes the development and metastasis of breast cancer by interacting with estrogen and ER,and it may become a new direction for breast cancer endocrine therapy.
文摘Colorectal cancer(CRC)is a type of cancer that grows from polypoid lesions developing over the years.It has a high incidence of about 1.8 million new cases annually.While screening and lifestyle modifications have stabilized the rate of CRC in high-income countries,the incidence of early-onset CRC is increasing globally.The worst prognosis for this cancer is linked to recurrence and metastasis,with peritoneal metastasis occurring in 8%to 20%of cases.In these cases,treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is indicated.However,this approach is risky and requires careful selection of patients who will truly benefit from it.This article will discuss the correlation between nutrition and inflammation in patients with peritoneal metastasis and advanced CRC,emphasizing the importance of nutritional and inflammatory markers for assessing disease status.Finally,we will highlight the main biomarkers in the field.
基金Supported by National Natural Science Foundation of China,No.82270634.
文摘As one of the most prevalent malignant tumors,hepatocellular carcinoma(HCC)represents a major global public health burden.Traditionally,HCC pathogenesis has been attributed to chronic liver diseases(viral hepatitis,cirrhosis)and aflatoxin exposure.However,with evolving lifestyles and environmental changes,sleep disorders have become increasingly prevalent.Emerging evidence suggest that sleep disorders may contribute to hepatocarcinogenesis through multiple mechanisms,including immunity environment disorder,oxidative stress,metabolic dysregulation,disruption of gut microbiota,and circadian rhythm disruption,thereby influencing disease progression and patient prognosis.This review summarizes epidemiological evidence on the relationship between sleep disorders and HCC incidence,explores the underlying mechanisms through which sleep disorders contribute to HCC,and discusses clinical challenges and potential intervention strategies.Our objective is to provide novel insights into HCC prevention and therapeutic approaches.
基金Supported by the Debbie’s Dream Foundation-AACR Gastric Cancer Research Fellowship under grant number 16-40-41-MART to HMan Institutional Development Award(IDeA)from the National Institute of General Medical Sciences of the National Institutes of Health(NIH)under grant number P20GM103395 to HM,NS and MO
文摘AIM To evaluate recent trends in gastric cancer incidence, response to treatment, and overall survival among Alaska Native(AN) people. METHODS A retrospective analysis of the Alaska Native Medical Center patient database was performed. Patient history, clinical, pathological, response to treatment and patient outcomes were collected from one-hundred and thirty-two AN gastric cancer patients. The Surveillance, Epidemiology and End Result database 18 was used to collect comparison United States non-Hispanic White(NHW) and AN gastric cancer patient data between 2006-2014.RESULTS AN gastric cancer patients have a higher incidence rate, a poorer overall survival, and are diagnosed at a significantly younger age compared to NHW patients. AN patients differ from NHW patients in greater prevalence of non-cardia, diffuse subtype, and signet ring cell carcinomas. AN females were more likely to be diagnosed with later stage cancer, stage IV, compared to AN males. Diminished overall survival was observed among AN patients with increasing stage, O+ blood type, < 15 lymph nodes examined at resection, and no treatment. This study is the first report detailing the clinicopathologic features of gastric cancer in AN people with outcome data.CONCLUSION Our findings confirm the importance of early detection, treatment, and surgical resection for optimizing AN patient outcomes. Further research on early detection markers are warranted.
基金Supported by NIH R01 CA169702-01A1(to Zheng L)NIH K23 CA148964-01(to Zheng L)+6 种基金Johns Hopkins School of Medicine Clinical Scientist Award(to Zheng L)Viragh Foundation and the Skip Viragh Pancreatic Cancer Center at Johns Hopkins(to Zheng L)The National Pancreas Foundation(to Zheng L)Lefkofsky Family Foundation(to Zheng L)the NCI SPORE in Gastrointestinal Cancers P50 CA062924(to Zheng L)Lustgarten Foundation(to Zheng L)the Sol Goldman Pancreatic Cancer Center grants(to Zheng L)
文摘Pancreatic ductal adenocarcinoma(PDA)is among the deadliest cancers in the United States and in the world.Late diagnosis,early metastasis and lack of effective therapy are among the reasons why only 6%of patients diagnosed with PDA survive past 5 years.Despite development of targeted therapy against other cancers,little progression has been made in the treatment of PDA.Therefore,there is an urgent need for the development of new treatments.However,in order to proceed with treatments,the complicated biology of PDA needs to be understood first.Interestingly,majority of the tumor volume is not made of malignant epithelial cells but of stroma.In recent years,it has become evident that there is an important interaction between the stromal compartment and the less prevalent malignant cells,leading to cancer progression.The stroma not only serves as a growth promoting source of signals but it is also a physical barrier to drug delivery.Understanding the tumor-stroma signaling leading to development of desmoplastic reaction and tumor progression can lead to the development of therapies to decrease stromal activity and improve drug delivery.In this review,we focus on how the current understanding of biology of the pancreatic tumor microenvironment can be translated into the development of targeted therapy.
基金supported by Mayo Clinic Foundation(MC-HH999 to Haojie Huang).
文摘Prostate cancer(PCa)is the most commonly diagnosed cancer among men in western countries.Androgen receptor(AR)signaling plays key roles in the development of PCa.Androgen deprivation therapy(ADT)remains the standard therapy for advanced PCa.In addition to its ligand androgen,accumulating evidence indicates that posttranscriptional modification is another important mechanism to regulate AR activities during the progression of PCa,especially in castration resistant prostate cancer(CRPC).To date,a number of posttranscriptional modifications of AR have been identified,including phosphorylation(e.g.by CDK1),acetylation(e.g.by p300 and recognized by BRD4),methylation(e.g.by EZH2),ubiquitination(e.g.by SPOP),and SUMOylation(e.g.by PIAS1).These modifications are essential for the maintenance of protein stability,nuclear localization and transcriptional activity of AR.This review summarizes posttranslational modifications that influence androgen-dependent and-independent activities of AR,PCa progression and therapy resistance.We further emphasize that in addition to androgen,posttranslational modification is another important way to regulate AR activity,suggesting that targeting AR posttranslational modifications,such as proteolysis targeting chimeras(PROTACs)of AR,represents a potential and promising alternate for effective treatment of CRPC.Potential areas to be investigated in the future in the field of AR posttranslational modifications are also discussed.
基金Supported by The Capital Health Development Special Scientific Research Projects,No.2014-2-2154National Natural Science Foundation of China,No.81471761 and No.81501568
文摘AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected in 527 individuals, including 115 healthy control(HC), 198 colorectal adenoma(CA), and 214 CC individuals in the training group. RESULTS Serum TFF3 showed no significant correlation with age, gender, or tumor location but showed significant correlation with the tumor stage. Serum TFF3 in the CC group was significantly higher than in the HC or CA group. The AUC values of TFF3 for discriminating between HC and CC and between CA and CC were 0.930(0.903, 0.958) and 0.834(0.796, 0.873). A multivariate model combining TFF3 and CEA was built. Compared to TFF3 or CEA alone, the multivariate model showed significant improvement(P < 0.001). For discriminating between HC and CC, HC and early stage CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%, 93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%, 93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%, respectively. CONCLUSION The multivariate diagnostic model that included TFF3 and CEA showed significant improvement over the conventional biomarker CEA and might provide a potential method for the early detection of CC.
基金The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.
文摘Objective Gastric cancer(GC)is a deadly cancer and a challenging public health problem globally.This study aimed to analyze potential genes associated with pathogenesis and prognosis of gastric cancer.Methods This work selected the overlapping differentially expressed genes(DEGs)in GC from four datasets,the GSE29272,GSE29998,GSE54129 and GSE118916 Gene Expression Omnibus databases.These DEGs were used to carry out comprehensive bioinformatic analysis to analyze the related functions and pathways enriched,the relative expression levels and immune infiltrates,the prognostic characteristics and the interaction network.Results In total,55 DEGs increased while 98 decreased in their expression levels.For those DEGs with increased expression,they were mostly concentrated on“focal adhesion”and“ECM-receptor interaction”,whereas DEGs with decreased expression were mostly associated with“gastric acid secretion”and“drug metabolism cytochrome P450”.MCODE and ClueGO results were then integrated to screen 10 hub genes,which were FN1,COL1A1,COL3A1,BGN,TIMP1,COL1A2,LUM,VCAN,COL5A2 and SPP1.Survival analysis revealed that higher expression of the ten hub genes significantly predicted lower overall survival of GC patients.TIMP1 was most significantly related to neutrophils,CD8+T cells,as well as dendritic cells,while LUM was most significantly related to macrophages.Conclusion Immunohistochemistry results and functional testing showed that the expression of COL5A2 was elevated in GC and that it might be a key gene in GC tumorigenesis.
文摘BACKGROUND Gemcitabine plus platinum is the standard of care first-line treatment for advanced biliary tract cancers(BTC).There is no established second-line therapy,and retrospective reviews report median progression-free survival(PFS)less than 3 mo on second-line therapy.5-Fluorouracil plus irinotecan(FOLFIRI)is a commonly used regimen in patients with BTC who have progressed on gemcitabine plus platinum,though there is a paucity of data regarding its efficacy in this population.AIM To assess the efficacy of FOLFIRI in patients with biliary tract cancers.METHODS We retrospectively identified patients with advanced BTC who were treated with FOLFIRI at MD Anderson,University of Michigan and Mayo Clinic in Jacksonville.Data were collected on patient demographics,BTC subtype,response per RECIST v1.1,progression and survival.RESULTS Ninety-eight patients were included of which 74(75%)had metastatic and 24(25%)had locally advanced disease at the time of treatment with FOLFIRI.The median age was 60(range,22-86)years.The number of patients with extrahepatic cholangiocarcinoma,gall bladder cancer and intrahepatic cholangiocarcinoma were 10,17 and 71,respectively.FOLFIRI was used as 1st,2nd,3rd or 4th–Nth lines in 8,50,36 and 4 patients,respectively.Median duration on FOLFIRI in the entire cohort was 2.2(range,0.5-8.4)mo.The median PFS and overall survival were 2.4(95%confidence interval(CI):1.7-3.1)and 6.6(95%CI:4.7-8.4)mo,respectively.Median PFS for patients treated with FOLFIRI in 1st,2nd,3rd or 4th–Nth lines were 3.1,2.5,2.3 and 1.5 mo,respectively.Eighteen patients received concurrent bevacizumab(n=13)or EGFR-targeted therapy(n=5)with FOLFIRI,with a median PFS of 2.7 mo(95%CI:1.7-5.1).CONCLUSION In this largest multi-institution retrospective review of 98 patients with BTC treated with FOLFIRI,efficacy appears to be modest with outcomes similar to other cytotoxic chemotherapy regimens.
文摘Recent studies showed that inflammation is a critical cause for initiation and/or development of many cancers. In prostate cancer(PC), the inflammatory cells usually populate an immune-competent organ. This inflammatory organ can be involved in the initiation and progression of PC. Here, we mainly focus on the role of inflammation in the PC and progression of castration-resistant PC(CRPC). Moreover, we summarize the roles of inflammation factors(such as chemokines and cytokines) in PC and CRPC. Taken together, this review gives an insight into therapy for PC and CRPC through anti-inflammation.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81770283,No.81902018 and No.82070302)。
文摘Objective:The eukaryotic release factor 3a(eRF3a),a member of the eukaryotic peptide chain release factor family,is overexpressed in several types of cancer.This study aims to investigate the biological role and mechanism of eRF3a in the progression of liver cancer.
基金supported in part by grants from the National Natural Science Foundation of China(No.81072152 and No.81770283)Natural Science Foundation of Hubei Province(No.2015CFA027)+3 种基金Research Foundation of Health and Family Planning Commission of Hubei Province(No.WJ2015MAO10 and No.WJ2017M249)Clinical Medical Research Center of Peritoneal Cancer of Wuhan(No.2015060911020462)Subsidy Project of No.1 Hospital of Lanzhou University(No.Idyyyn2018-13)Innovation fund of universities in Gansu Province(No.2020B-009).
文摘Objective:The present study was aimed to identify novel key genes,prognostic biomarkers and molecular pathways implicated in tumorigenesis of colon cancer.Methods:The microarray data GSE41328 containing 10 colon cancer samples and 10 adjacent normal tissues was analyzed to identify 4763 differentially expressed genes.Meanwhile,another microarray data GSE17536 was performed for weighted gene co-expression network analysis(WGCNA).Results:In present study,12 co-expressed gene modules associated with tumor progression were identified for further studies.The red module showed the highest association with pathological stage by Pearson's correlation analysis.Functional enrichment analysis revealed that genes in red module focused on cell division,cell proliferation,cell cycle and metabolic related pathway.Then,a total of 26 key hub genes were identified,and GEPIA database was subsequently selected for validation.Holliday junction-recognizing protein(HJURP)and cell division cycle 25 homolog C(CDC25C)were identified as effective prognosis biomarkers,which were all detrimental to prognosis.Gene set enrichment analyses(GSEA)found the two hub genes were enriched in“oocyte meiosis”,“oocyte maturation that are progesterone-mediated”,“p53 signaling pathway”,and“cell cycle”.Furthermore,the immunohistochemistry and western blotting showed that HJURP was highly expressed in colon cancer tissue.Conclusion:HJURP was identified as a key gene associated with colon cancer progression and prognosis by WGCNA,which might influence the prognosis by regulating cell cycle pathways.
文摘Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.
文摘The androgen receptor （AR） is a pleio-trophic transcription factor that regu-lates expression of a large number of genes involved in many diverse cellular processes. The AR activation pathways have been studied extensively. However, the molecular mechanism and biological significance of AR inhibitory signals remain poorly understoo＆ Mukhopadhyay et aL have now identified the nuclear matrix protein scaffold attachmenl factor B1 （SAFB1） as a novel AR corepressor. The authors found that SAFB1 physically associates with AR protein and inhibits AR transcriptional activity and androgen-sens- itive gene expression. SAFB1 had no effect on chromatin occupancy of AR, but silencin of SAFB1 abolished recruitment MST1, known AR repressor, at AR target loci. The also showed that SAFB1 interacts with EZH2 SUZ12 and EED, three core components o the Polycomb repressive complex 2 （PRC2）, which catalyzes the gene repression histone modification H3 lysine 27 trimethylation （H3K27me3）. The authors further showed that forced expression of SAFB1 increases H3K27me3 at AR target loci and this effec requires EZH2. Finally, the authors demon strated that expression of SAFB1 is downre-guiated in human prostate cancer （PCa） specimens and SAFB1 knockdown results in an aggressive phenotype of PCa. These find-ings identify SAFB1 as an important node for integration of multiple inhibitory signals ot AR, which represents a viable pathway fol therapeutic intervention of PCa.
文摘In sub-Saharan Africa, breast cancer (BC) constitutes a serious public health problem and the genetic basis of its development is remaining poorly understood. Although the SNPs at codon 72 of <em>TP</em>53 (rs1042522) and at the UTR of <em>SET</em>8 (rs16917496) have both been associated with BC development among Asian and European women, no published data has been reported within African population. We herein report on the impact of these polymorphisms on the risk of BC among Cameroonian women. Blood samples were collected from 111 breast cancer patients and 224 controls. DNA was extracted from each sample and PCR-RFLP was used to investigate the polymorphisms at SNPs rs1042522 of <em>TP</em>53 and rs16917496 of <em>SET</em>8. Association studies were performed according to ethno-linguistic groups and menopausal status. The minor allele “T” of <em>SET</em>8 gene revealed a protective effect in premenopausal women (OR, 0.327;95% CI 0.125 - 0.852) while the CT genotype of <em>SET</em>8 was associated with increased risk of BC (OR, 2.93;95% CI, 1.1 - 7.8). The minor “G” allele of <em>TP</em>53 gene was significantly associated (OR, 2.533;95% CI, 1.455 - 4.408) with increased disease risk in premenopausal women while the CG genotype was significantly associated (OR, 0.39;95% CI, 0.23 - 0.69) with decreased risk of BC. A synergistic genetic interaction at both loci for CC genotype of SET8 and CG genotype of <em>TP</em>53 was associated (OR, 0.46;95% CI, 0.24 - 0.91) with reduced disease risk. No significant association between polymorphisms at the SET8 and <em>TP</em>53 loci and clinical pathologic features of BC was observed. This study suggests significant associations between the SNPs located at the 3’-UTR of <em>SET</em>8 and codon 72 of the <em>TP</em>53 with the risk of breast cancer development among premenopausal women. There is an interaction between <em>TP</em>53 and <em>SET</em>8 genes.
基金This study was supported by Guangxi Medical and Health Appropriate Technology Development and Application Project(No.S2019075)Self-financed Program by Health and Family Planning Commission of Guangxi Zhuang Autonomous Region(No.Z20180748).
文摘Background:Elevated levels of circulating endothelial cells might reflect significant vascular damage and dysfunction.Recent studies have shown that circulating endothelial cells levels are related to therapeutic responses of tumors,and thus,could be used as an indicator to predict the efficacy of tumor treatments.The purpose of this study was to investigate the correlation and impact of endothelial cells with and on the efficacy of first-line therapy(platinum-based or tyrosine kinase inhibitor drugs treatments)for advanced non-small-cell lung cancer.Methods:We analyzed 45 inpatients who met the inclusion criteria of diagnosis with inoperable non-small-cell lung cancer stages III and IV,in the People’s Hospital of Guangxi Zhuang Autonomous Region from January 2019 to January 2020.The flow cytometry technique was adopted to detect pretreatment levels of circulating endothelial cells in peripheral blood of patients with advanced non-small-cell lung cancer.The pretreatment peripheral blood was collected to analyze the relations of circulating endothelial cells with different clinical characteristics and efficacy.Results:The level of pretreatment circulating endothelial cells was significantly correlated with the efficacy of treatment(P<0.05)but irrelevant to the patient’s physical conditions,pathological type,tumor stage,and pretreatment serum carcinoembryonic antigen(P>0.05).The comparison between the groups of response(complete response+partial response)and nonresponse(stable disease+progressive disease)showed a significant difference in circulating endothelial cells count.Compared with low levels of circulating endothelial cells,a high level of circulating endothelial cells led to a poor efficacy(P<0.05).Conclusion:The level of pretreatment circulating endothelial cells significantly correlated with the efficiency of first-line therapy for non-small-cell lung cancer.Compared with low level of circulating endothelial cells,high level of circulating endothelial cells lead to poor efficacy.Therefore,circulating endothelial cell is indeed an effective indicator for predicting the efficacy of first-line therapy for advanced non-small-cell lung cancer.
文摘Newer systemic therapies for hepatocellular carcinoma(HCC)have led to growing interest in combining hepatic arterial infusion chemotherapy(HAIC)with systemic treatments.To evaluate the effectiveness and safety of HAIC and combination therapies in treating advanced HCC,a network meta-analysis was conducted by Zhou et al.The study included data from 44 articles.HAIC was superior in overall survival(OS),progression-free survival(PFS),and response rates compared to transarterial chemoembolization and sorafenib.Moreover,combinations of HAIC with other treatments and single agents(e.g.,lenvatinib,ablation,anti-programmed cell death 1 therapy,radiotherapy)provided better OS and PFS outcomes than HAIC alone.In this editorial,we will discuss the study findings,the strengths and weaknesses of the metanalysis,and future advances in the field of HAIC for advanced HCC.
基金supported in part by the National Cancer Institute under award numbers R01CA268287A1,U01CA269181,R01CA26820701A1,R01CA249992-01A1,R01CA202752-01A1,R01CA208236-01A1,R01CA216579-01A1,R01CA220581-01A1,R01CA257612-01A1,1U01CA239055-01,1U01CA248226-01,1U54CA254566-01National Heart,Lung and Blood Institute 1R01HL15127701A1,R01HL15807101A1+8 种基金National Institute of Biomedical Imaging and Bioengineering 1R43EB028736-01VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service the Office of the Assistant Secretary of Defense for Health Affairs,through the Breast Cancer Research Program(W81XWH-19-1-0668)the Prostate Cancer Research Program(W81XWH-20-1-0851)the Lung Cancer Research Program(W81XWH-18-1-0440,W81XWH-20-1-0595)the Peer Reviewed Cancer Research Program(W81XWH-18-1-0404,W81XWH-21-1-0345,W81XWH-211-0160)the Kidney Precision Medicine Project(KPMP)Glue Grant and sponsored research agreements from Bristol Myers-Squibb,Boehringer-Ingelheim,Eli-Lilly and Astrazenecasupported in part by the National Natural Science Foundation of China general program(No.61571314)the Sichuan University-Yibin City Strategic Cooperation Special Fund(No.2020CDYB-27)Support Program of Sichuan Science and Technology Department(No.2023YFS0327-LH).
文摘Accurate prognosis prediction is essential for guiding cancer treatment and improving patient outcomes.While recent studies have demonstrated the potential of histopathological images in survival analysis,existing models are typically developed in a cancerspecific manner,lack extensive external validation,and often rely on molecular data that are not routinely available in clinical practice.To address these limitations,we present PROGPATH,a unified model capable of integrating histopathological image features with routinely collected clinical variables to achieve pancancer prognosis prediction.PROGPATH employs a weakly supervised deep learning architecture built upon the foundation model for image encoding.Morphological features are aggregated through an attention-guided multiple instance learning module and fused with clinical information via a cross-attention transformer.A router-based classification strategy further refines the prediction performance.PROGPATH was trained on 7999 whole-slide images(WSIs)from 6,670 patients across 15 cancer types,and extensively validated on 17 external cohorts with a total of 7374 WSIs from 4441 patients,covering 12 cancer types from 8 consortia and institutions across three continents.PROGPATH achieved consistently superior performance compared with state-of-the-art multimodal prognosis prediction models.It demonstrated strong generalizability across cancer types and robustness in stratified subgroups,including early-and advancedstage patients,treatment cohorts(radiotherapy and pharmaceutical therapy),and biomarker-defined subsets.We further provide model interpretability by identifying pathological patterns critical to PROGPATH’s risk predictions,such as the degree of cell differentiation and extent of necrosis.Together,these results highlight the potential of PROGPATH to support pancancer outcome prediction and inform personalized cancer management strategies.
