Tsunedomi Ryouichi, Iizuka Norio, Yamada-Okabe Hisafumi, Tamesa Takao, Okada Toshimasa, Sakamoto Kazuhiko, Takashima Motonari, Hamaguchi Takeshi, Miyamoto Takanobu, Uchimura Shunji, Hamamoto Yoshihiko, Yamada Mamoru, Oka Masaaki
Department of Digestive Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Int J Oncol. 2006 Dec;29(6):1445-51.
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.
门静脉侵犯（PVI）是肝细胞癌（HCC）转移潜能的一个标志，且在中度分化的HCC阶段经常出现。为了鉴定与丙型肝炎病毒（HCV）相关的HCC的PVI中涉及的基因，我们通过DNA微阵列对35例中度分化的HCV相关HCC中的12600个基因进行了全面分析。我们的监督学习方法鉴定出了35个与PVI相关的基因。在这35个鉴定出的基因中，我们聚焦于DNA结合抑制因子2（ID2），因为它编码一种肝脏富集的显性负性螺旋-环-螺旋蛋白。ID2的微阵列结果通过定量实时逆转录（QRT）-PCR和蛋白质印迹分析得以重现。在一组独立的HCV相关HCC（n = 28）和HCV无关HCC（n = 14）中，我们的QRT-PCR显示，ID2 mRNA水平的降低与HCV相关HCC中的PVI相关，但与HCV无关HCC无关。总之，我们的结果强烈表明ID2在HCV相关HCC的PVI过程中起重要作用。
