Identification of ETV5 as a Prognostic Marker Related to Epigenetic Modification in Pan-Cancer and Facilitates Tumor Progression in Hepatocellular Carcinoma

Sep 21, 2026

ETS variant transcription factor 5 (ETV5) is investigated as a prognostic biomarker linked to epigenetic modification across multiple cancers. Integrated mining uses TCGA and GTEx RNA-seq data with clinical and pathological features to assess associations between ETV5 expression, patient outcomes, drug sensitivity, and epigenetic regulators. Results show abnormally high ETV5 predicts unfavorable prognosis and altered drug sensitivity in several malignancies, and correlates with EZH2-mediated epigenetic modulation. In hepatocellular carcinoma, ETV5 aligns with advanced pathological stage and drives adverse outcomes.

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CategoryResearch & Report

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ETV5 expression profile and its association with prognosis evaluation in pan-cancer

ETV5 analysis using TCGA across multiple cancer types

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Identification of ETV5 as a prognostic marker related to epigenetic modification in pancancer and facilitates tumor progression in hepatocellular carcinoma Hongmeng Su1, Luyu Zhao1, Tianle Fang1, Wenhao Han2 & Hong Fan1􀀍 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. Keywords ETV5, Pan-cancer, Hepatocellular carcinoma, Epigenetic modification, Integrated analysis As a worldwide disease problem, cancer poses a serious threat to human health due to its high incidence and mortality rate. It was estimated that the global cancer incidence will exceed 28.4 million annually, accounting for one in six deaths by 20401,2. The current treatment methods for tumors mainly include surgical resection, radiation therapy, chemotherapy3, targeted therapy4 and immunotherapy5. However, the heterogeneity of the tumors, individual patient variability6 and drug resistance during treatment7,8 lead to unsatisfactory therapeutic outcomes. With the development of epigenetics and epitranscriptomics, epigenetic therapy, a potential treatment for highly aggressive tumors, offers new hope for patients9. Single-cell sequencing and multi-omics analysis also revealed the importance of epigenetic modification in tumor heterogeneity. Currently, inhibitors targeting epigenetic modification modulators DNMTs, HDACs, and EZH2 have been approved by the FDA for various malignancies treatment, including 5-azacytidine, decitabine, romidepsin, vorinostat, belinostat, panobinostat and tazemetostat10. Besides, several inhibitors of LSD1, BET and DOT1L are also employed in experimental and preclinical researches to explore better anti-tumor effect10, 11. The tumorigenesis and tumor progression are accompanied by abnormal regulation of multiple genes, including transcription factors. ETS is one of the largest transcription factor families and involved in various developmental and physiological processes. It has been reported that ETS family members interact with 1Department of Medical Genetics and Developmental Biology, School of Medicine, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, China. 2School of Life Science and Technology, Southeast University, Nanjing, China. 􀀍 email: [fanh@seu.edu.cn](fanh@seu.edu.cn) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) chromatin remodeling complexes to regulate the chromatin accessi

FAQs

What relationship does ETV5 expression show with prognosis in multiple cancers?

Abnormally high ETV5 expression is associated with unfavorable prognosis across multiple malignancies in the integrated analyses.

Which epigenetic modification regulator is linked to ETV5 in this study?

ETV5 expression is associated with epigenetic modification modulators, specifically including EZH2.

How does ETV5 influence tumor progression in hepatocellular carcinoma?

In hepatocellular carcinoma, ETV5 expression correlates with tumor pathological stage and is linked to adverse patient outcomes, and ETV5 promotes cell proliferation while reducing sensitivity to GSK126 through regulation of EZH2.

Sep 21, 2026

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