Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression

Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression
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DOI:
10.1002/ijc.22605
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发表时间:
2007-07-01
影响因子:
6.4
通讯作者:
Mori, Masaki
Mori, Masaki
中科院分区:
医学1区
文献类型:
--
作者:
Ieta, Keisuke;Ojima, Eiki;Mori, Masaki

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本研究包括两个目的:(1)通过基因芯片分析确定与肝细胞癌相关的基因;(2)评价基因芯片分析发现的人泛素结合酶E2C(Ube2c)在肝细胞癌中过表达的临床病理意义。采用激光显微切割和基因芯片技术筛选与肝癌相关的基因。然后我们将重点放在Ube2c基因上。应用实时定量逆转录聚合酶链式反应(RT-PCR)技术,检测65例临床肝细胞癌组织中Ube2c的表达情况及临床病理意义。与非癌肝细胞相比,在肝癌细胞中发现了一些上调的基因,其中之一是Ube2c基因。65例癌组织中有62例Ube2c基因表达高于癌旁组织(95.4%,P<0.01)。Ube2c高表达的肿瘤侵袭到包膜形成(FC-inf)、侵袭门静脉(VP)和肿瘤去分化的频率较高(p&lt;0.05)。Ube2c高表达患者的无病生存率也明显低于Ube2c低表达患者(p&lt;0.01)。此外,在多因素分析中,Ube2c表达被发现是无病生存率的独立预后因素。我们发现了肝细胞癌和正常肝组织之间的差异表达基因。其中,Ube2c基因似乎与肝细胞癌的进展有关,并可能作为肝细胞癌患者的预后指标。(C)2007年Wiley-Liss,Inc.
This study consisted of 2 aims: (i) to determine genes associated with hepatocellular carcinoma (HCC) by microarray analysis; and (ii) to evaluate the clinicopathological significance of human ubiquitin-conjugating enzyme E2C (Ube2c) found to be overexpressed in HCC from microarray analysis. Laser microdissection and cDNA-microarray were performed to identify genes associated with HCC. We then focused on the Ube2c gene. Using realtime quantitative reverse transcription-polymerase chain reaction (RT-PCR), Ube2c expression status and clinicopathological significance were studied in 65 clinical HCC samples. A number of genes upregulated in HCC cells compared to noncancerous liver cells were identified, one of which was the Ube2c gene. Ube2c gene expression in the cancer tissue was higher than in the corresponding noncancerous tissue in 62 of the 65 cases (95.4%, p < 0.01). Tumors with high Ube2c expression showed higher frequencies of tumor invasion to capsular formation (fc-inf), invasion to portal vein (vp) and tumor de-differentiation (p < 0.05). Patients with high Ube2c expression also showed significantly worse disease-free survival rates than those with low Ube2c expression (p < 0.01). In addition, Ube2c expression was found to be an independent prognostic factor for disease-free survival rate in multivariate analysis. We identified differentially expressed genes between HCC and normal liver tissues. Of those, the Ube2c gene appeared to be associated with HCC progression, and may be useful as a prognostic indicator for HCC patients. (C) 2007 Wiley-Liss, Inc.