Systematic pan-cancer analysis reveals the prognostic and immunological roles of ectonucleoside triphosphate diphosphohydrolase 6.

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.