Genome-wide methylation profiling identified novel differentially hypermethylated biomarker MPPED2 in colorectal cancer

作者：Simeng Gu, Shujuan Lin, Ye Ding, Sangni Qian, Danjie Jiang, Xiaocong Zhang, Qilong Li, Jinhua Yang, Xiaojiang Ying, Zhenjun Li, Mengling Tang, Jianbing Wang, Mingjuan Jin, Kun Chen · 发表于：Clinical Epigenetics · 年份：2019 · DOI：10.1186/s13148-019-0628-y · 被引用次数：40 · 研究领域：Epigenetics and DNA Methylation、Genetic factors in colorectal cancer、Ferroptosis and cancer prognosis

BACKGROUND: Epigenetic alternation is a common contributing factor to neoplastic transformation. Although previous studies have reported a cluster of aberrant promoter methylation changes associated with silencing of tumor suppressor genes, little is known concerning their sequential DNA methylation changes during the carcinogenetic process. The aim of the present study was to address a genome-wide search for identifying potentially important methylated changes and investigate the onset and pattern of methylation changes during the progression of colorectal neoplasia. METHODS: A three-phase design was employed in this study. In the screening phase, DNA methylation profile of 12 pairs of colorectal cancer (CRC) and adjacent normal tissues was analyzed by using the Illumina MethylationEPIC BeadChip. Significant CpG sites were selected based on a cross-validation analysis from The Cancer Genome Atlas (TCGA) database. Methylation levels of candidate CpGs were assessed using pyrosequencing in the training dataset (tumor lesions and adjacent normal tissues from 46 CRCs) and the validation dataset (tumor lesions and paired normal tissues from 13 hyperplastic polyps, 129 adenomas, and 256 CRCs). A linear mixed-effects model was used to examine the incremental changes of DNA methylation during the progression of colorectal neoplasia. RESULTS: The comparisons between normal and tumor samples in the screening phase revealed an extensive CRC-specific methylomic pattern with 174,006 (21%)...