Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers

Genome Medicine
Jinming ChengYixue Li

Abstract

Hepatocellular carcinoma (HCC) is the one of the most common cancers and lethal diseases in the world. DNA methylation alteration is frequently observed in HCC and may play important roles in carcinogenesis and diagnosis. Using the TCGA HCC dataset, we classified HCC patients into different methylation subtypes, identified differentially methylated and expressed genes, and analyzed cis- and trans-regulation of DNA methylation and gene expression. To find potential diagnostic biomarkers for HCC, we screened HCC-specific CpGs by comparing the methylation profiles of 375 samples from HCC patients, 50 normal liver samples, 184 normal blood samples, and 3780 samples from patients with other cancers. A logistic regression model was constructed to distinguish HCC patients from normal controls. Model performance was evaluated using three independent datasets (including 327 HCC samples and 122 normal samples) and ten newly collected biopsies. We identified a group of patients with a CpG island methylator phenotype (CIMP) and found that the overall survival of CIMP patients was poorer than that of non-CIMP patients. Our analyses showed that the cis-regulation of DNA methylation and gene expression was dominated by the negative correlatio...Continue Reading

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Citations

Sep 6, 2019·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Xuedong WangYu Chang
May 13, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Xiaokang WangXiongzhi Wu
Mar 30, 2019·Cancer Cell International·Zhongyi ShenJinxia Liu
Jul 10, 2019·Experimental and Therapeutic Medicine·Ka WangShiyuan Xu
Nov 11, 2020·Cancer Control : Journal of the Moffitt Cancer Center·Wenhai HuangPeisong Chen
Dec 4, 2020·Nucleic Acids Research·Hsi-Yuan HuangHsien-Da Huang
Sep 22, 2020·Pathology, Research and Practice·Qichen LiuZhong Chen
Apr 4, 2021·International Journal of Molecular Sciences·Lok-Sze Wong, Chun-Ming Wong
Apr 6, 2021·Current Hepatology Reports·Adeniji Nia, Renumathy Dhanasekaran
Mar 14, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Léa MeunierEric Letouzé

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Datasets Mentioned

BETA
GSE56588
GSE69270

Methods Mentioned

BETA
PCR
biopsies
electrophoresis
enough

Software Mentioned

edgeR
WEKA
R package ConsensusClusterPlus
Bioconductor

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