Identification of novel candidate tumour marker genes for intrahepatic cholangiocarcinoma
Identification of novel candidate tumour marker genes for intrahepatic cholangiocarcinoma
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DOI：
10.1016/j.jhep.2008.03.025
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发表时间：
2008-08-01
影响因子：
25.7
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
--
作者：
Nishino, Ryuhei;Honda, Masao;Kaneko, Shuichi
背景/目的：肝内胆管癌（ICC）的早期检测和诊断需要特异性标志物；然而，目前使用的肿瘤标志物对ICC并无特异性。
方法：我们通过基因表达系列分析（SAGE）比较了ICC的cDNA文库和肝细胞癌（HCC）的cDNA文库。通过对74个样本（包括16个ICC样本）进行实时定量逆转录聚合酶链反应（RT - PCR）、免疫印迹和免疫组化分析，确认了每种样本中的表达模式。
结果：对两个文库的比较揭示了每种肝癌类型独特的基因表达模式。除了已知的肿瘤标志物外，我们还检测到9个与ICC相关的新基因。通过比较ICC文库中的平均转录本丰度与其他文库（包括胃癌、结肠癌、前列腺癌和乳腺癌）中的平均转录本丰度，以及我们的RT - PCR结果，我们确定了3个基因作为ICC的特异性标志物：双糖链蛋白聚糖、胰岛素样生长因子结合蛋白5和紧密连接蛋白4。免疫印迹和免疫组化分析表明紧密连接蛋白4在ICC中高表达。此外，判别分析显示，这些基因的组合可用于区分ICC与HCC或转移性腺癌。
结论：我们确定了ICC的新型标志物基因，这些基因可能对肝癌的诊断有用。（C）2008年欧洲肝脏研究协会。由爱思唯尔出版集团出版。保留所有权利。
Background/Aims: Specific markers are required for early detection and diagnosis of intrahepatic cholangiocarcinoma (ICC); however, the tumour markers currently in use are not specific for ICC.Methods: We compared an ICC cDNA library with that of hepatocellular carcinoma (HCC) by serial analysis of gene expression (SAGE). The expression patterns in each were confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting and immunohistochemical analysis of 74 samples including 16 ICC samples.Results: A comparison of the two libraries revealed distinct gene expression patterns for each type of liver cancer. In addition to the known tumour markers, we detected nine novel genes associated with ICC. By comparing the mean transcript abundance in the ICC library with those in other libraries, including gastric, colon, prostate and breast cancer, together with our RT-PCR results, we identified three genes as specific markers of ICC: biglycan, insulin-like growth factor-binding protein 5 and claudin-4. Immunoblotting and immunohistochemical analyses showed that claudin-4 was highly expressed in ICC. Moreover, discrimination analysis revealed that a combination of these genes could be used to distinguish ICC from HCC or metastatic adenocarcinoma.Conclusions: We identified novel marker genes of ICC that are potentially useful for the diagnosis of liver cancer. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.