Effect of increased levels of ID2 on progression of hepatocellular carcinoma

本研究的目的是探讨DNA结合/分化抑制因子2（Inhibitor of DNA binding/differentiation 2，ID 2）的分子生物学功能。(1)为了验证我们以前的DNA微阵列研究的表达模式，我们通过实时逆转录PCR测量了92例HCC新队列中ID 2 mRNA的水平。ID 2 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。ID 2水平低的患者比ID 2水平高的患者具有显著更差的预后。(2)To为了阐明ID 2的确切作用，我们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ID 2对HCC细胞侵袭潜力的抑制作用，这可以部分地通过改变MMP和一些血管生成相关蛋白的水平和/或分泌来解释。Int J Oncol，2006）。此外，我们结合上述结果（（1）和（2））提交了一篇论文。此外，HCC研究的相关发现在全球5种科学医学期刊上报道。

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.