A Novel Gene Prognostic Signature Based on Differential DNA Methylation in Breast Cancer

作者：Chunmei Zhu, Shuyuan Zhang, Di Liu, Qingqing Wang, Ningning Yang, Zhewen Zheng, Qiuji Wu, Yunfeng Zhou · 发表于：Frontiers in Genetics · 年份：2021 · DOI：10.3389/fgene.2021.742578 · 被引用次数：46 · 研究领域：Epigenetics and DNA Methylation、Ferroptosis and cancer prognosis、Cancer Genomics and Diagnostics

Background: DNA methylation played essential roles in regulating gene expression. The impact of DNA methylation status on the occurrence and development of cancers has been well demonstrated. However, little is known about its prognostic role in breast cancer (BC). Materials: The Illumina Human Methylation450 array (450k array) data of BC was downloaded from the UCSC xena database. Transcriptomic data of BC was downloaded from the Cancer Genome Atlas (TCGA) database. Firstly, we used univariate and multivariate Cox regression analysis to screen out independent prognostic CpGs, and then we identified methylation-associated prognosis subgroups by consensus clustering. Next, a methylation prognostic model was developed using multivariate Cox analysis and was validated with the Illumina Human Methylation27 array (27k array) dataset of BC. We then screened out differentially expressed genes (DEGs) between methylation high-risk and low-risk groups and constructed a methylation-based gene prognostic signature. Further, we validated the gene signature with three subgroups of the TCGA-BRCA dataset and an external dataset GSE146558 from the Gene Expression Omnibus (GEO) database. Results: We established a methylation prognostic signature and a methylation-based gene prognostic signature, and there was a close positive correlation between them. The gene prognostic signature involved six genes: IRF2, KCNJ11, ZDHHC9, LRP11, PCMT1, and TMEM70. We verified their expression in mRNA and prote...