Research analyzing ETV5 expression across 26 cancer types from The Cancer Genome Atlas (TCGA) reveals significant overexpression in 14 tumor types, including colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), and liver hepatocellular carcinoma (LIHC). Conversely, lung adenocarcinoma (LUAD), breast invasive carcinoma (BRCA), and prostate adenocarcinoma (PRAD) exhibited lower ETV5 levels.
Univariate Cox regression indicated that high ETV5 expression correlates with worse overall survival (OS) in patients with LIHC, lower grade glioma, and pancreatic adenocarcinoma (PAAD). Additionally, disease-specific survival (DSS) analysis showed similar trends, particularly in GBMLGG and KIPAN cohorts.
ETV5 localization primarily occurs in the nucleus, suggesting its role in transcriptional regulation. Investigations into DNA methylation of the ETV5 promoter revealed hypomethylation in tumor tissues, implying that methylation may not be the primary mechanism for ETV5 overexpression.
Further analysis identified a positive correlation between ETV5 and DNA methyltransferases, indicating a potential role in regulating oncogenes through epigenetic modifications. ETV5 expression also correlated with RNA methylation and histone modification regulators, suggesting its involvement in diverse regulatory processes affecting tumorigenesis.
Gene ontology analysis of ETV5-related genes highlighted their participation in tumor progression pathways, including the ERK and MAPK signaling pathways. ETV5 expression was linked to decreased sensitivity to various anticancer drugs, particularly in hepatocellular carcinoma (HCC) cells, where high ETV5 levels were associated with poor treatment outcomes.
In HCC patient samples, ETV5 was highly expressed in 75% of tumors, correlating with increased tumor size and malignancy. Survival analysis indicated that patients with elevated ETV5 levels experienced significantly shorter OS durations.
ETV5's association with EZH2, a methyltransferase linked to poor prognosis in HCC, suggests a collaborative role in tumor progression. Targeting ETV5 may enhance the efficacy of EZH2 inhibitors, presenting a potential therapeutic strategy for HCC.