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An integrated analysis of genome-wide DNA methylation and gene expression data in hepatocellular carcinoma.

ABSTRACT: Despite progress in the treatment of hepatocellular carcinoma (HCC), 5-year survival rates remain low. Thus, a more comprehensive approach to explore the mechanism of HCC is needed to provide new leads for targeted therapy. We performed an integrated analysis to discover the relationship between DNA methylation and gene expression in hepatocellular carcinoma (HCC). DNA methylation and gene expression data for HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and differential analysis was performed. Correlation analysis between DNA methylation and gene expression data was then performed in R language. Finally, we selected several crucial genes and evaluated their potential use as diagnostic biomarkers for HCC. In total, 1135 differentially DNA-methylated CpG sites (DMCs), 377 differentially methylated regions (DMRs), and 1194 differentially expressed genes (DEGs) were identified in HCC. Among the DEGs, 14 genes (ALX3, B4GALNT1,CTHRC1,DLX5,EMX1,IRX3,OTX1,SIX2,TLX1,VASH2,ZIC2,ZIC4,ZIC5, and ZNF695) exhibited changes in DNA methylation in terms of CpG sites or CpG island (CGI) level, of which TLX1 and ZIC4 had the most DMCs (12 and 13, respectively). Further analysis of CTHRC1,ZIC4,SIX2,VASH2,IL17D,TLX1,OTX1, and LART, examining alterations in both DNA methylation and gene expression level in HCC, showed their potential diagnostic value for HCC was better at the gene expression level than that the DNA methylation level. The DNA methylation status of CTHRC1,VASH2, and IL7D was significantly associated with HCC overall survival (P-value <0.05). This systemic analysis identified a group of novel gene signatures (CTHRC1,ZIC4, and OTX1) that may be regulated by DNA hypermethylation, which may be closely associated with HCC.

SUBMITTER: Sun XJ

PROVIDER: S-EPMC6026698 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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An integrated analysis of genome-wide DNA methylation and gene expression data in hepatocellular carcinoma.

Sun Xiang-Jun XJ Wang Ming-Chun MC Zhang Feng-Hua FH Kong Xiao X

FEBS open bio 20180530 7

Despite progress in the treatment of hepatocellular carcinoma (HCC), 5-year survival rates remain low. Thus, a more comprehensive approach to explore the mechanism of HCC is needed to provide new leads for targeted therapy. We performed an integrated analysis to discover the relationship between DNA methylation and gene expression in hepatocellular carcinoma (HCC). DNA methylation and gene expression data for HCC were downloaded from The Cancer Genome Atlas (TCGA) database, and differential anal ...[more]

PMID: 29988590

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Project description:Hepatocellular carcinoma (HCC) incidence has increased in the US and also has one of the fastest growing death rates of any cancer. The purpose of the current study was to discover novel genome-wide aberrant DNA methylation patterns in HCC tumors that are predominantly HCV-related. Infinium HumanMethylation 450K BeadChip arrays were used to examine genome-wide DNA methylation profiles in 66 pairs of HCC tumor and adjacent non-tumor tissues. After Bonferroni adjustment, a total of 130,512 CpG sites significantly differed in methylation level in tumor compared with non-tumor tissues, with 28,017 CpG sites hypermethylated and 102,495 hypomethylated in tumor tissues. Absolute tumor/non-tumor methylation differences ? 20% were found in 24.9% of the hypermethylated and 43.1% of the hypomethylated CpG sites; almost 10,000 CpG sites have ? 30% DNA methylation differences. Most (60.1%) significantly hypermethylated CpG sites are located in CpG islands, with 21.6% in CpG shores and 3.6% in shelves. In contrast, only a small proportion (8.2%) of significantly hypomethylated CpG sites are situated in islands, while most are found in open sea (60.2%), shore (17.3%) or shelf (14.3%) regions. A total of 2,568 significant CpG sites (2,441 hypermethylated and 127 hypomethylated) covering 589 genes are located within 684 differentially methylated regions defined as regions with at least two significant CpG sites displaying > 20% methylation differences in the same direction within 250-bp. The top 500 significant CpG sites can significantly distinguish HCC tumor from adjacent tissues with one misclassification. Within adjacent non-tumor tissues, we also identified 75 CpG sites significantly associated with gender, 228 with HCV infection, 17,207 with cirrhosis, and 56 with both HCV infection and cirrhosis after multiple comparisons adjustment. Aberrant DNA methylation profiles across the genome were identified in tumor tissues from US HCC cases that are predominantly related to HCV infection. These results demonstrate the significance of aberrant DNA methylation in HCC tumorigenesis.

Dataset Information

An integrated analysis of genome-wide DNA methylation and gene expression data in hepatocellular carcinoma.

Publications

An integrated analysis of genome-wide DNA methylation and gene expression data in hepatocellular carcinoma.

Similar Datasets

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