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

作者：Wang, Xiaoshuai; Yu, Jingwei; Chen, Jinbao; Hou, Yingdong; Du, Zefeng; Huang, Haoyang; Tang, Siqi; Han, Yueyin; Ding, Changhai; Xue, Zhicheng^*

来源：Cancer Medicine, 2021, 10(21): 7804-7815.

DOI：10.1002/cam4.3981

• bladder cancer
• copy number variation
• immune cells
• N-6-methyladenosine
• prognosis

Purpose Growing evidence has demonstrated an indispensable role for N-6-methyladenosine (m(6)A) in human diseases, but the copy number variations (CNVs) of m(6)A regulatory genes in bladder cancer (BLCA) remains largely unknown. Methods We investigated the CNVs on all known m(6)A 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 m(6)A regulatory genes and immune infiltrates was analyzed by The Tumor Immune Estimation Resource (TIMER) database. Results CNV events of m(6)A 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 m(6)A regulatory genes were correlated with specific kinds of immune infiltrates. Conclusions There are significant correlations between m(6)A regulatory genes with CNVs and clinicopathological characteristics. METTL3 with CNVs were associated with the immune infiltrates and performed as a prognostic marker in BLCA.

• 单位
  中山大学; 南方医科大学