Effect of increased levels of ID2 on progression of hepatocellular carcinoma

DNA结合/分化抑制剂2 （Inhibitor of DNA binding/differentiation 2, ID2）在先前的肝细胞癌（HCC）门静脉侵袭（PVI）相关基因全基因组搜索中被发现与门静脉侵袭（PVI）有关，本研究旨在探讨ID2的分子和生物学功能。(1)为了验证我们之前的DNA微阵列研究中的表达模式，我们通过实时逆转录- pcr测量了92个hcc新队列中的ID2 mRNA水平。ID2 mRNA水平与PVI （P < 0.001）、TNM分期（P < 0.001）、肿瘤大小（P < 0.001）、早期肝内复发（P < 0.05）呈负相关。低水平ID2患者的预后明显差于高水平ID2患者。(2)为了明确ID2的确切作用，我们利用表达载体和小干扰rna进行了体外分析。这些基因靶向实验揭示了ID2对HCC细胞侵袭潜力的抑制作用，这可以部分解释为改变MMPs和一些血管生成相关蛋白的水平和/或分泌。我们报道了id2mrna水平与HCC进展之间的关系（Tsunedomi et al.，《国际肿瘤学杂志》，2006）。此外，我们将结合上述结果(1)和(2)提交一篇论文。此外，HCC研究的相关发现在全球5个科学医学期刊上发表。

The purpose of this study is to explore the molecular and biologic functions of Inhibitor of DNA binding/differentiation 2 (ID2), which was found to be responsible for portal vein invasion (PVI) of hepatocellular carcinoma (HCC) in a previous genome-wide search for the PVI-related genes.(1) To validate the expression pattern on our previous DNA microarray study, we measured ID2 mRNA levels in a new cohort of 92 HCCs by real-time reverse transcription-PCR. ID2 mRNA level correlated inversely with PVI (P < 0.001), TNM stage (P < 0.001), tumor size (P < 0.001), and early intrahepatic recurrence (P < 0.05). Patients with low levels of ID2 had significantly poorer prognoses than those with high levels of ID2.(2)To clarify the precise roles of ID2, we performed in vitro analysis with expression vectors and small interfering RNAs. These gene-targeting experiments revealed inhibitory effects of ID2 on the invasive potential of HCC cells, which could be explained in part by altering levels and/or secretion of MMPs and some angiogenesis-related proteins.We reported the relation between ID2 mRNA levels and progression of HCC (Tsunedomi et al., Int J Oncol, 2006). Moreover, we are submitting a paper in combination with the above results ((1) and (2)). Also, the relevant findings on HCC research were reported in 5 scientific medical journals worldwide.