Comparison of gene expression profiles between Opisthorchis viverrini and non-Opisthorchis viverrini associated human intrahepatic cholangiocarcinoma
Comparison of gene expression profiles between Opisthorchis viverrini and non-Opisthorchis viverrini associated human intrahepatic cholangiocarcinoma
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DOI：
10.1002/hep.21330
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发表时间：
2006-10-01
期刊：
影响因子：
13.5
通讯作者：
Nakamura, Yusuke
中科院分区：
文献类型：
--
作者：
Jinawath, Natini;Chamgramol, Yaovalux;Nakamura, Yusuke
肝内胆管癌（ICC）是第二大常见的原发性肝癌，其发病率在泰国东北部最高。已知该地区的icc与肝吸虫感染，特别是毒弧菌（OV）以及食物中的亚硝胺有关。为了阐明与肝吸虫相关或不相关的ICC的分子机制，我们分析了来自20名泰国患者的OV相关ICC的基因表达谱，并通过激光微束显微解剖和包含27,648个基因的cDNA微阵列，将其与20名与OV无关的日本ICC的基因表达谱进行了比较。我们在两个ICC组中鉴定了77个普遍上调的基因和325个普遍下调的基因。无监督层次聚类分析几乎完全根据薄片状态将40个icc分成两大分支。ov相关ICC的推定特征表现为参与外源代谢的基因（UGT2B11, UGT1A10, CHST4, SULT1C1）的表达升高，而非ov相关ICC则表现为与生长因子信号相关的基因（TGFBI， PGF, IGFBP1, IGFBP3）的表达增强。另外的随机排列测试确定了49个基因的表达水平在两组之间有显著差异。我们还鉴定了与宏观类型icc相关的基因。总之，这些数据可能不仅有助于阐明ICC的常见机制和ov特异性机制，而且可能作为鉴定该疾病的新诊断标记或治疗靶点的起点。
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary cancer in the liver, and its incidence is highest in the northeastern part of Thailand. ICCs in this region are known to be associated with infection with liver flukes, particularly Opisthorchis viverrini (OV), as well as nitrosamines from food. To clarify molecular mechanisms of ICC associated with or without liver flukes, we analyzed gene expression profiles of OV-associated ICCs from 20 Thai patients and compared their profiles with those of 20 Japanese ICCs that were not associated with OV, by means of laser microbeam microdissection and a cDNA microarray containing 27,648 genes. We identified 77 commonly upregulated genes and 325 commonly downregulated genes in the two ICC groups. Unsupervised hierarchical cluster analysis separated the 40 ICCs into two major branches almost completely according to the flake status. The putative signature of OV-associated ICC exhibited elevated expression of genes involved in xenobiotic metabolism (UGT2B11, UGT1A10, CHST4, SULT1C1), whereas that of non-OV-associated ICC represented enhanced expression of genes related to growth factor signaling (TGFBI, PGF, IGFBP1, IGFBP3). Additional random permutation tests identified a total of 49 genes whose expression levels were significantly different between the two groups. We also identified genes associated with macroscopic type of ICCs. In conclusion, these data may not only contribute to clarification of common and OV-specific mechanisms underlying ICC, but also may serve as a starting point for the identification of novel diagnostic markers or therapeutic targets for the disease.