Copy number variation analysis of m6A regulators identified METTL3 as a prognostic and immune‐related biomarker in bladder cancer

Abstract

Abstract Purpose Growing evidence has demonstrated an indispensable role for N6‐methyladenosine (m6A) in human diseases, but the copy number variations (CNVs) of m6A regulatory genes in bladder cancer (BLCA) remains largely unknown. Methods We investigated the CNVs on all known m6A regulatory genes using the Cancer Genome Atlas (TCGA) database. The association between CNV events and clinicopathological as well as molecular characteristics of BLCA patients were explored. Gene set enrichment analysis (GSEA) was implemented to reveal relative cellular processes. Association between m6A regulatory genes and immune infiltrates was analyzed by The Tumor Immune Estimation Resource (TIMER) database. Results CNV events of m6A regulatory genes were frequently observed in BLCA. CNVs of METTL3, METTL14, and METTL16 correlated with molecular characteristics of BLCA patients including TP53 mutation. CNVs of METTL3 associated with the overall survival (OS) of BLCA patients. METTL3 was also associated with several cancer‐related cellular processes, including mitotic spindle assembly, G2/M checkpoint, and E2F targets signaling pathway. Besides, the CNVs of m6A regulatory genes were correlated with specific kinds of immune infiltrates. Conclusions There are significant correlations between m6A regulatory genes with CNVs and clinicopathological characteristics. METTL3 with CNVs were associated with the immune infiltrates and performed as a prognostic marker in BLCA.

Keywords

• bladder cancer
• copy number variation
• immune cells
• N6‐methyladenosine
• prognosis