Malignant diseases in both children and adults are a worldwide public health priority with a high socioeconomic burden.Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6)molecule exhibits divergent expression pat...Malignant diseases in both children and adults are a worldwide public health priority with a high socioeconomic burden.Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6)molecule exhibits divergent expression patterns across different cancers.Its increased expression in some tumors may allow them to escape anti-tumor immune responses,potentially by inducing an immunosuppressive tumor microenvironment and favoring a poorer prognosis.Conversely,in vivo,a mutated ENTPD6 gene may induce effective cytotoxic T cell responses,thereby reducing liver tumor size.Additionally,low expression of ENTPD6 has been related to chemotherapy resistance,whereas specific ENTPD6-derived neoepitopes may potentially enhance the efficacy of immunotherapy.This paper analyses the dual roles and clinical utility of ENTPD6 in cancer.展开更多
BACKGROUND Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6),a member of the ENTPD family,has been implicated in certain cancers,yet a comprehensive analysis across multiple cancer types remains lacking.AIM To ...BACKGROUND Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6),a member of the ENTPD family,has been implicated in certain cancers,yet a comprehensive analysis across multiple cancer types remains lacking.AIM To systematically evaluate ENTPD6’s expression,prognostic significance,and functions across multiple cancer types.METHODS In this study,we performed a pan-cancer analysis to investigate the correlation between ENTPD6 expression and various factors,including prognosis,genetic alterations,epigenetic modification,immune infiltration,immunotherapy responses,functional enrichment,and drug sensitivity.A tissue microarray of gastrointestinal tumors was used to validate differential ENTPD6 protein expression.RESULTS Pan-cancer analysis revealed that ENTPD6 expression was significantly elevated in many cancers.Immunohistochemistry staining analysis revealed that ENTPD6 expression was significantly higher in esophageal carcinoma,stomach adenocarcinoma,colon adenocarcinoma,rectal adenocarcinoma,and pancreatic adenocarcinoma compared to normal tissues.Furthermore,ENTPD6 expression was strongly associated with immune-infiltrating cells,particularly clusters of differentiation 8+T cells and natural killer cells,and correlated with immune-related genomic features including tumor mutational burden and microsatellite instability.Pathway analysis indicated that ENTPD6 expression was primarily linked to purine and pyrimidine metabolism pathways.Drug sensitivity analysis revealed that high ENTPD6 expression was sensitive to RDEA119,selumetinib,and PD-0325901.CONCLUSION This pan-cancer study elucidates the pivotal role of ENTPD6 in tumor progression and establishes its potential as a therapeutic target for immunotherapeutic approaches in specific malignancies.展开更多
文摘Malignant diseases in both children and adults are a worldwide public health priority with a high socioeconomic burden.Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6)molecule exhibits divergent expression patterns across different cancers.Its increased expression in some tumors may allow them to escape anti-tumor immune responses,potentially by inducing an immunosuppressive tumor microenvironment and favoring a poorer prognosis.Conversely,in vivo,a mutated ENTPD6 gene may induce effective cytotoxic T cell responses,thereby reducing liver tumor size.Additionally,low expression of ENTPD6 has been related to chemotherapy resistance,whereas specific ENTPD6-derived neoepitopes may potentially enhance the efficacy of immunotherapy.This paper analyses the dual roles and clinical utility of ENTPD6 in cancer.
基金Supported by the Science and Technology Program of Gansu Province,No.23JRRA1015the International Science and Technology Cooperation Project of Gansu Provincial Science and Technology Department,No.2023YFWA0009the Innovation and Entrepreneurship Project for Young Talents of Lanzhou Science and Technology Bureau,No.2023-4-18.
文摘BACKGROUND Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6),a member of the ENTPD family,has been implicated in certain cancers,yet a comprehensive analysis across multiple cancer types remains lacking.AIM To systematically evaluate ENTPD6’s expression,prognostic significance,and functions across multiple cancer types.METHODS In this study,we performed a pan-cancer analysis to investigate the correlation between ENTPD6 expression and various factors,including prognosis,genetic alterations,epigenetic modification,immune infiltration,immunotherapy responses,functional enrichment,and drug sensitivity.A tissue microarray of gastrointestinal tumors was used to validate differential ENTPD6 protein expression.RESULTS Pan-cancer analysis revealed that ENTPD6 expression was significantly elevated in many cancers.Immunohistochemistry staining analysis revealed that ENTPD6 expression was significantly higher in esophageal carcinoma,stomach adenocarcinoma,colon adenocarcinoma,rectal adenocarcinoma,and pancreatic adenocarcinoma compared to normal tissues.Furthermore,ENTPD6 expression was strongly associated with immune-infiltrating cells,particularly clusters of differentiation 8+T cells and natural killer cells,and correlated with immune-related genomic features including tumor mutational burden and microsatellite instability.Pathway analysis indicated that ENTPD6 expression was primarily linked to purine and pyrimidine metabolism pathways.Drug sensitivity analysis revealed that high ENTPD6 expression was sensitive to RDEA119,selumetinib,and PD-0325901.CONCLUSION This pan-cancer study elucidates the pivotal role of ENTPD6 in tumor progression and establishes its potential as a therapeutic target for immunotherapeutic approaches in specific malignancies.
