title: Genes associated with recurrence of hepatocellular carcinoma: integrated analysis by gene expression and methylation profiling.
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.
authors: Miles and Shirley Fiterman Center for Digestive Diseases, College of Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Ju Dong
authors: JD
authors: Yang
authors: So-Young
authors: SY
authors: Seol
authors: Sun-Hee
authors: SH
authors: Leem
authors: Yong Hoon
authors: YH
authors: Kim
authors: Zhifu
authors: Z
authors: Sun
authors: Ju-Seog
authors: JS
authors: Lee
authors: Snorri S
authors: SS
authors: Thorgeirsson
authors: In-Sun
authors: IS
authors: Chu
authors: Lewis R
authors: LR
authors: Roberts
authors: Koo Jeong
authors: KJ
authors: Kang
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000096:biosynthesis; D059467:Transcriptome / Q000235:genetics
chemical_list: D012333:RNA, Messenger