EZH2 is a negative prognostic biomarker associated with immunosuppression in hepatocellular carcinoma

• Published in: PloS one Vol. 15; no. 11; p. e0242191
• Main Authors: Guo, Baoping, Tan, Xiaohong, Cen, Hong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.11.2020; Public Library of Science (PLoS)
• Subjects: Antigen presentation; Antigens; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; Care and treatment; Chemotherapy; Datasets; Diagnosis; Enhancer of Zeste Homolog 2 Protein - genetics; Enhancer of Zeste Homolog 2 Protein - metabolism; Gene expression; Gene set enrichment analysis; Genomics; Glycolysis; Health aspects; Hepatocellular carcinoma; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Homology; Humans; Immunosuppression; Immunotherapy; Interferon; Interferon-gamma - genetics; Interferon-gamma - metabolism; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Medical prognosis; Medicine and Health Sciences; Melanoma; Metastases; Methods; mRNA; Mutation; Myc protein; Patients; Proteins; Signal transduction; Signaling; Survival; Survival analysis; Tumor Microenvironment - immunology; Variance analysis; γ-Interferon; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0242191

The enhancer of zeste homolog 2 (EZH2) plays a critical role in different components of anti-tumor immunity. However, the specific role of EZH2 in modulating MHC Class I antigen presentation and T cell infiltration have not been investigated in HCC. This study analyzed the expression and clinical significance of EZH2 in HCC. The EZH2 genetic alterations were identified using cBioPortal. The EZH2 mRNA and protein levels were found to be significantly higher in HCC than in adjacent normal liver tissues in multiple datasets from the GEO and TCGA databases. High expression of EZH2 was significantly correlated with poor overall survival, disease-specific survival, progression-free survival, and relapse-free survival in almost all patients with HCC. The gene set variance analysis (GSVA) showed that the expression of EZH2 is positively correlated with an immunosuppressive microenvironment and negatively correlated with major MHC class I antigen presentation molecules. Gene set enrichment analysis (GSEA) showed that high EZH2 expression is positively associated with the MYC and glycolysis signaling pathway and negatively associated with the interferon-gamma signaling pathway in HCC tissues. These findings demonstrate that EZH2 is a potential prognostic biomarker and therapeutic target in HCC.