An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single-base resolution methylome and hydroxymethylome
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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.
In: Clinical and Translational Medicine, Vol. 11, No. 7, e498, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single-base resolution methylome and hydroxymethylome
AU - Han, Yingxin
AU - Ji, Liyan
AU - Guan, Yanfang
AU - Ma, Mengya
AU - Li, Pansong
AU - Xue, Yinge
AU - Zhang, Yinxin
AU - Huang, Wanqiu
AU - Gong, Yuhua
AU - Jiang, Li
AU - Wang, Xipeng
AU - Xie, Hong
AU - Zhou, Boping
AU - Wang, Jiayin
AU - Wang, Junwen
AU - Han, Jinghua
AU - Deng, Yuliang
AU - Yi, Xin
AU - Gao, Fei
AU - Huang, Jian
N1 - © 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Biomarkers, Tumor/genetics
KW - Cervical Intraepithelial Neoplasia/genetics
KW - CpG Islands
KW - DNA Copy Number Variations
KW - DNA Methylation
KW - Epigenomics
KW - Exoribonucleases/genetics
KW - Female
KW - Histones/genetics
KW - Humans
KW - Multienzyme Complexes/genetics
KW - Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics
KW - Signal Transduction
KW - Sulfate Adenylyltransferase/genetics
KW - Survival Rate
KW - Uterine Cervical Neoplasms/genetics
U2 - 10.1002/ctm2.498
DO - 10.1002/ctm2.498
M3 - Journal article
C2 - 34323415
VL - 11
JO - Clinical and Translational Medicine
JF - Clinical and Translational Medicine
SN - 2001-1326
IS - 7
M1 - e498
ER -
ID: 299205594