Identification of ID2 associated with invasion of hepatitis C virus-related hepatocellular carcinoma by gene expression profile
Tsunedomi, R.; Iizuka, N.; Yamada-Okabe, H.; Tamesa, T.; Okada, T.; Sakamoto, K.; Takashima, M.; Hamaguchi, T.; Miyamoto, T.; Uchimura, S.; Hamamoto, Y.; Yamada, M.; Oka, M.
International Journal of Oncology 29(6): 1445-1451
2006
ISSN/ISBN: 1019-6439 PMID: 17088983 Document Number: 595957
Portal vein invasion (PVI) is a hallmark of metastatic potential of hepatocellular carcinoma (HCC) and is frequently found at a stage of moderately differentiated HCC. To identify genes involved in PVI of HCC associated with hepatitis C virus (HCV), we performed a comprehensive analysis of 12,600 genes in 35 moderately differentiated HCV-related HCCs by DNA microarray. Our supervised learning method identified 35 genes involved in PVI. Among the 35 identified genes, we focused on the inhibitor of DNA binding 2 (ID2), because it encodes a liver-rich dominant-negative helix-loop-helix protein. The microarray results for ID2 were reproduced by quantitative real-time reverse transcription (QRT)-PCR and Western blot analyses. In an independent set of HCV-related HCCs (n=28) and HCV-unrelated HCCs (n=14), our QRT-PCR showed that decrease in ID2 mRNA levels were associated with PVI in HCV-related HCC but not HCV-unrelated HCC. In conclusion, our results strongly suggest that ID2 plays an important role in PVI process of HCV-related HCC.