Genes Associated with Recurrence of Hepatocellular Carcinoma: Integrated Analysis by Gene Expression and Methylation Profiling.
10.3346/jkms.2011.26.11.1428
- Author:
Ju Dong YANG
1
;
So Young SEOL
;
Sun Hee LEEM
;
Yong Hoon KIM
;
Zhifu SUN
;
Ju Seog LEE
;
Snorri S THORGEIRSSON
;
In Sun CHU
;
Lewis R ROBERTS
;
Koo Jeong KANG
Author Information
1. Miles and Shirley Fiterman Center for Digestive Diseases, College of Medicine, Mayo Clinic, Rochester, MN, USA. kjkang@dsmc.or.kr
- Publication Type:Original Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
- Keywords:
Carcinoma, Hepatocellular;
Gene Expression Profiling;
Microarray analysis;
DNA methylation;
Survival
- MeSH:
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
- From:Journal of Korean Medical Science
2011;26(11):1428-1438
- CountryRepublic of Korea
- Language:English
-
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.
