Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer worldwide [1]
We comprehensively examined the expression of enhancer of zeste homolog 2 (EZH2), its correlation with prognosis, and the status of different tumor-infiltrating immune cells based on data from patients with HCC in The Cancer Genome Atlas (TCGA) and various public databases
Significantly higher levels of EZH2 mRNA were observed in HCC tissues than in adjacent normal liver tissues from multiple GEO datasets (Fig 1B–1F)
Summary
Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer worldwide [1]. Because most patients are diagnosed in advanced stages, the 5-years overall survival rate is only 10% [2]. Current treatment options that include the use of sorafenib and regorafenib provide only marginal benefits for advanced HCC [3, 4]. Immunotherapy with anti-PD-1 antibodies like pembrolizumab has shown a substantial survival benefit in certain cancers, such as Hodgkin’s disease and melanoma [5, 6]. The success of immunotherapy has been much more limited in other cancer types, such as HCC [7]. There is a need to identify new therapies for the effective treatment of HCC
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