Abstract
Gene expression is suppressed by DNA methylation. The goal of this study was to identify genes whose CpG site methylation and mRNA expression are associated with recurrence after surgical resection for hepatocellular carcinoma (HCC). Sixty-two HCCs were examined by both whole genome DNA methylation and transcriptome analysis. The Cox model was used to select genes associated with recurrence. A validation was performed in an independent cohort of 66 HCC patients. Among fifty-nine common genes, increased CpG site methylation and decreased mRNA expression were associated with recurrence for 12 genes (Group A), whereas decreased CpG site methylation and increased mRNA expression were associated with recurrence for 25 genes (Group B). The remaining 22 genes were defined as Group C. Complement factor H (CFH) and myosin VIIA and Rab interacting protein (MYRIP) in Group A; proline/serine-rich coiled-coil 1 (PSRC1), meiotic recombination 11 homolog A (MRE11A), and myosin IE (MYO1E) in Group B; and autophagy-related protein LC3 A (MAP1LC3A), and NADH dehydrogenase 1 alpha subcomplex assembly factor 1 (NDUFAF1) in Group C were validated. In conclusion, potential tumor suppressor (CFH, MYRIP) and oncogenes (PSRC1, MRE11A, MYO1E) in HCC are reported. The regulation of individual genes by methylation in hepatocarcinogenesis needs to be validated.
Keywords
Carcinoma
Hepatocellular
DNA methylation
Gene Expression Profiling
Microarray analysis
Survival
MeSH Terms
Adult
Aged
Carcinoma, Hepatocellular/genetics,pathology,surgery
CpG Islands
DNA Methylation
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Liver/pathology
Liver Neoplasms/genetics,pathology,surgery
Male
Middle Aged
Neoplasm Recurrence, Local/genetics
Oligonucleotide Array Sequence Analysis
Proportional Hazards Models
RNA, Messenger/biosynthesis
Transcriptome/genetics
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Yang Ju Dong
Miles and Shirley Fiterman Center for Digestive Diseases, College of Medicine, Mayo Clinic, Rochester, MN, USA.
Seol So-Young
Leem Sun-Hee
Kim Yong Hoon
Sun Zhifu
Lee Ju-Seog
Thorgeirsson Snorri S
Chu In-Sun
Roberts Lewis R
Kang Koo Jeong
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