EZH2 is a biomarker associated with lung cancer diagnosis and immune infiltrates without prognostic specificity: a study based on the cancer genome atlas data*

Abstract

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2). Dysregulation of EZH2 causes alteration of gene expression and functions, thereby promoting cancer development. Recent studies suggest that EZH2 has a potential prognostic role in patients with non-small cell lung cancer (NSCLC). However, the prognostic value of EZH2 expression levels in NSCLC is controversial. In this study, we evaluated the prognostic value in lung cancer (LC-LUAD/LUSC) based on data from The Cancer Genome Atlas (TCGA) database. Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological features. Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors. Gene set enrichment analysis (GSEA) was performed to identify the key pathways related to EZH2. The correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set Enrichment Analysis (ssGSEA). EZH2 was found to be up regulated with amplification in tumor tissues in multiple LC cohorts. High EZH2 expression was associated with poorer overall survival (OS). GSEA suggested that EZH2 regulates innate immune system, ECM affiliated, matrisome, surfactant metabolism. Notably, ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2 cells and significantly negatively correlated with mast cell infiltration level. These results suggest that EZH2 is associated with LC immune infiltration and significantly over-expressed in lung cancer, and its diagnostic value is better than prognosis, which lays a foundation for further study of the immunomodulatory role of EZH2 in LC.