Open AccessAn epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome
Author(s) -
Han Yingxin,
Ji Liyan,
Guan Yanfang,
Ma Mengya,
Li Pansong,
Xue Yinge,
Zhang Yinxin,
Huang Wanqiu,
Gong Yuhua,
Jiang Li,
Wang Xipeng,
Xie Hong,
Zhou Boping,
Wang Jiayin,
Wang Junwen,
Han Jinghua,
Deng Yuliang,
Yi Xin,
Gao Fei,
Huang Jian
Publication year - 2021
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.498
Subject(s) - epigenetics , dna methylation , epigenomics , methylation , cpg site , biology , carcinogenesis , bisulfite sequencing , cervical cancer , cancer research , differentially methylated regions , computational biology , cancer , gene , genetics , gene expression
Background Cervical cancer (CC) is the second leading cause of cancer death among women worldwide. Epigenetic regulation of gene expression through DNA methylation and hydroxymethylation plays a pivotal role during tumorigenesis. In this study, to analyze the epigenomic landscape and identify potential biomarkers for CCs, we selected a series of samples from normal to cervical intra‐epithelial neoplasia (CINs) to CCs and performed an integrative analysis of whole‐genome bisulfite sequencing (WGBS‐seq), oxidative WGBS, RNA‐seq, and external histone modifications profiling data. Results In the development and progression of CC, there were genome‐wide hypo‐methylation and hypo‐hydroxymethylation, accompanied by local hyper‐methylation and hyper‐hydroxymethylation. Hydroxymethylation prefers to distribute in the CpG islands and CpG shores, as displayed a trend of gradual decline from health to CIN2, while a trend of increase from CIN3 to CC. The differentially methylated and hydroxymethylated region‐associated genes both enriched in Hippo and other cancer‐related signaling pathways that drive cervical carcinogenesis. Furthermore, we identified eight novel differentially methylated/hydroxymethylated‐associated genes ( DES, MAL, MTIF2, PIP5K1A, RPS6KA6, ANGEL2, MPP , and PAPSS2 ) significantly correlated with the overall survival of CC. In addition, no any correlation was observed between methylation or hydroxymethylation levels and somatic copy number variations in CINs and CCs. Conclusion Our current study systematically delineates the map of methylome and hydroxymethylome from CINs to CC, and some differentially methylated/hydroxymethylated‐associated genes can be used as the potential epigenetic biomarkers in CC prognosis.