Expression profiling in hepatocellular carcinoma with intrahepatic metastasis: identification of high-mobility group I(Y) protein as a molecular marker of hepatocellular carcinoma metastasis

Expression profiling in hepatocellular carcinoma with intrahepatic metastasis: identification of high-mobility group I(Y) protein as a molecular marker of hepatocellular carcinoma metastasis
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DOI:
10.2302/kjm.53.90
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发表时间:
2004-06-01
影响因子:
2
通讯作者:
Sakamoto, Michiie
Sakamoto, Michiie
中科院分区:
其他
文献类型:
--
作者:
Chuma, Makoto;Saeki, Norihisa;Sakamoto, Michiie

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肝细胞癌(Hepatocellular carcinoma,HCC)是人类最常见、最具侵袭性的恶性肿瘤之一。其高死亡率主要是肝内转移的结果。为了研究癌转移的详细遗传机制,我们使用寡核苷酸阵列比较了20例肝内转移的HCC和10例无肝内转移的HCC的表达谱。在分析的约12600个基因中,我们确定了34个基因的表达水平与肝内转移显著相关(P < 0.05)。在这些基因中,我们进一步研究了高迁移率族I(Y)(HMG-I(Y))蛋白的表达。实时定量逆转录聚合酶链反应(RT-PCR)证实HMG-I(Y)在有肝内转移的HCC中表达上调,与无肝内转移的HCC相比。免疫组化结果显示,HMG-I(Y)在有肝内转移的HCC中的表达明显高于无肝内转移的HCC(P < 0.05)。这些结果表明,有肝内转移的肝癌和无肝内转移的肝癌的分子特征明显不同。HMG-I(Y)表达与肝内转移有关,可作为HCC肝内转移的预测指标。
Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies. Its high mortality rate is mainly a result of intra-hepatic metastases. To investigate the detailed genetic mechanisms in cancer metastasis, we compared the expression profiles of 20 HCCs with intrahepatic metastasis and 10 HCCs without intrahepatic metastasis using an oligonucleotide array. Of the approximately 12600 genes that were analyzed, we identified 34 genes whose expression levels were significantly correlated with intrahepatic metastasis (P < 0.05). Of these genes, we further investigated the expression of high-mobility group I(Y) (HMG-I(Y)) protein. Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed that HMG-I(Y) was up-regulated in HCC with intrahepatic metastasis, compared to its level in HCC without intrahepatic metastasis. Further immunohistochemical examination of HMG-I(Y) revealed a significant overexpression in HCC with intrahepatic metastasis, compared with that in HCC without intrahepatic metastasis (P < 0.05). These results indicate that the molecular signatures of HCC with intrahepatic metastasis and of HCC without intrahepatic metastasis are clearly different. HMG-I(Y) expression was associated with intrahepatic metastasis and may be a predictive marker of HCC intrahepatic metastasis.