An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single-base resolution methylome and hydroxymethylome.

Abstract

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.

• Authors: Yingxin Han, Liyan Ji, Yanfang Guan, Mengya Ma, Pansong Li, Yinge Xue, Yinxin Zhang, Wanqiu Huang, Yuhua Gong, Li Jiang, Xipeng Wang, Hong Xie, Boping Zhou, Jiayin Wang, Junwen Wang, Jinghua Han, Yuliang Deng, Xin Yi, Fei Gao, Jian Huang
• Journal: Clinical and translational medicine (Clin Transl Med) Vol. 11 Issue 7 Pg. e498 (07 2021) ISSN: 2001-1326 [Electronic] United States
• PMID: 34323415 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

Chemical References

• Biomarkers, Tumor
• Histones
• MAL protein, human
• Multienzyme Complexes
• Myelin and Lymphocyte-Associated Proteolipid Proteins
• PAPS synthetase
• Sulfate Adenylyltransferase
• ANGEL2 protein, human
• Exoribonucleases

Topics

• Biomarkers, Tumor (genetics)
• CpG Islands
• DNA Copy Number Variations
• DNA Methylation
• Epigenomics
• Exoribonucleases (genetics)
• Female
• Histones (genetics, metabolism)
• Humans
• Multienzyme Complexes (genetics)
• Myelin and Lymphocyte-Associated Proteolipid Proteins (genetics)
• Signal Transduction
• Sulfate Adenylyltransferase (genetics)
• Survival Rate
• Uterine Cervical Neoplasms (genetics, mortality, pathology)
• Uterine Cervical Dysplasia (genetics, mortality, pathology)