Journal
JOURNAL OF KOREAN MEDICAL SCIENCE
Volume 26, Issue 11, Pages 1428-1438Publisher
KOREAN ACAD MEDICAL SCIENCES
DOI: 10.3346/jkms.2011.26.11.1428
Keywords
Carcinoma; Hepatocellular; Gene Expression Profiling; Microarray analysis; DNA methylation; Survival
Categories
Funding
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology (MEST), Republic of Korea [2009-0063260]
- KRIBB
- Shared Research Equipment Assistance Program
- Korea Basic Science Institute
- MEST
- NIH [CA100882, CA128633]
- National Research Foundation of Korea [2008-0062003] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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