Abstract
ETS variant transcription factor 5 (ETV5), a master transcription factor during development, exerts vital function on the occurrence and progression of various cancers. In order to systematically analyze and explore ETV5 potential specific regulatory mechanisms in pan-cancer, RNA sequencing data and clinicopathological features of patients with various tumors were obtained through the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, and an integrated data mining analysis was carried out, including the association of ETV5 expression with patient prognosis, drug sensitivity and epigenetic modification. The results revealed that abnormally highly expressed ETV5 resulted in unfavorable prognosis and differential drug sensitivity in multiple malignancies, and its expression was associated with epigenetic modification modulators including EZH2. ETV5 related genes were enriched in tumorigenesis biological processes and signaling pathways. In hepatocellular carcinoma, ETV5 expression was correlated with patients' tumor pathological stage and resulted in adverse outcome of patients. Our further experiments evidences indicated that ETV5 facilitated cell proliferation and reduced sensitivity to GSK126 via regulating EZH2. Collectively, this study comprehensively elucidates the carcinogenic effects and molecular mechanisms of ETV5 in tumorigenesis and development, and provides theoretical basis and guidance for tumor diagnosis, targeted therapy for ETV5 and clinical epigenetic drug research.