Identifying Key Genes for Nasopharyngeal Carcinoma by Prioritized Consensus Differentially Expressed Genes Caused by Aberrant Methylation

作者：Yunqin Chen, Chun Yan Zhou, Hua‐Bin Li, Hong Li, Yixue Li · 发表于：Journal of Cancer · 年份：2020 · DOI：10.7150/jca.49392 · 被引用次数：45 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Epigenetics and DNA Methylation

Background: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy.Large-scale genetics or epigenetics studies of NPC have been relatively scarce and sporadic, and there are no effective targeted drugs for NPC.Integrative analysis of multiple different omics profiles has been proved to be an effective approach to shed new light on cancer.Methods: We developed a pipeline to aggregate consensus differentially expressed genes (DEGs) from multiple expression datasets from different platforms.Integrated bioinformatics analysis of DNA methylation and gene expression was used to prioritize key genes in NPC.We explored the biological and clinical importance of key genes, combining differential co-expression analysis, network analysis of protein-protein and microRNA (miRNA)-target interactions, and pan-cancer survival analysis.Results: We obtained 668 upregulated and 594 downregulated consensus DEGs, which enriched in the PI3K-AKT, NF-κB and immune-related pathways.In NPC, 98% of 3364 differentially methylated sites were hypermethylated.Actively expressed EBV gene EBNA1 was positively correlated with over-expressed genes coding DNA methyltransferase and Polycomb group proteins, suggesting that EBV infection may have an important role in the hypermethylation of NPC.Through integrated analysis of DNA methylation and mRNA and miRNA expression profiles, we prioritized 56 hypermethylated downregulated genes, including 7 tumor suppressor genes, and co...