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

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 poten...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288011/
https://www.ncbi.nlm.nih.gov/pubmed/34323415
http://dx.doi.org/10.1002/ctm2.498
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author 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
author_facet 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
author_sort Han, Yingxin
collection PubMed
description 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.
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spelling pubmed-82880112021-07-21 An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome 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 Clin Transl Med Research Articles 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. John Wiley and Sons Inc. 2021-07-19 /pmc/articles/PMC8288011/ /pubmed/34323415 http://dx.doi.org/10.1002/ctm2.498 Text en © 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
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
An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome
title An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome
title_full An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome
title_fullStr An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome
title_full_unstemmed An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome
title_short An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome
title_sort epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single‐base resolution methylome and hydroxymethylome
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288011/
https://www.ncbi.nlm.nih.gov/pubmed/34323415
http://dx.doi.org/10.1002/ctm2.498
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