Clinical Significance of Upregulation of EZH1 Expression in Hepatocellular Carcinoma Tissues

Abstract

Abstract Purpose The incidence and mortality of hepatocellular carcinoma (HCC) are increasing. It is urgent to develop more effective HCC biomarkers for diagnosis and treatment. This project intends to explore the expression of the enhancer of zeste 1 polycomb repressive complex 2 subunit (EZH1) and its mechanism in HCC. Methods This study integrates global microarray and high-throughput sequencing datasets, combined with internal immunohistochemistry, to analyze the expression and prognostic value of EZH1 in HCC. Functional enrichment analysis was conducted to investigate transcriptional targets, which were achieved by intersecting HCC over-expressed genes and EZH1 co-expressed genes, putative transcriptional targets. The relationship between EZH1 and anticancer drugs was detected by drug sensitivity analysis. Results In this study, 84 datasets from 40 platforms (3926 HCC samples and 3428 non-cancerous liver tissues) were included to show the high expression of EZH1 in HCC. Immunohistochemistry with 159 HCC samples and 62 non-HCC samples confirmed a high expression level. HCC patients with high EZH1 expression had worse survival prognoses. GO and Reactome analysis revealed that metabolism-related pathways, including autophagy, are critical for HCC. Interestingly, as one of the EZH1 potential transcriptional targets, autophagy-related 7 (ATG7) appeared in the above pathways. ATG7 was positively correlated with EZH1, upregulated in HCC, and mediated poor prognosis. Upregulation of EZH1 was found to be in contact with HCC anti-tumor drug resistance. Conclusion The upregulation of EZH1 expression can promote the occurrence of HCC and lead to poor clinical progression and drug resistance, these effects may be mediated by regulating ATG7.