Differentially expressed gene profiles of intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and combined hepatocellular-cholangiocarcinoma by integrated microarray analysis
Differentially expressed gene profiles of intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and combined hepatocellular-cholangiocarcinoma by integrated microarray analysis
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通过整合微阵列分析肝内胆管癌、肝细胞癌和混合性肝细胞胆管癌的差异表达基因谱。
DOI：
10.1007/s13277-015-3261-1
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发表时间：
2015-08-01
期刊：
影响因子：
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通讯作者：
Ren, Zheng-Gang
中科院分区：
文献类型：
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作者：
Xue, Tong-Chun;Zhang, Bo-Heng;Ren, Zheng-Gang
肝内胆管癌（ICC）和肝细胞癌（HCC）是世界范围内常见的原发性肝癌。然而，ICC的生存率和预后均比HCC差得多，这表明ICC与HCC之间存在不同的分子特征和机制。为了识别 ICC 和 HCC 或合并肝细胞胆管癌 (CHC) 之间的差异表达 (DE) 基因，我们对 MetaOmics 公开的微阵列基因表达综合 (GEO) 数据集进行了综合分析。三个 GEO 数据集（包括 32 个 ICC 生物芯片、77 个 HCC 生物芯片和 34 个 CHC 生物芯片）可用于数据集成。我们鉴定了 ICC 和 HCC 之间的 7313 个 DE 基因，其中包括 3650 个上调基因和 3663 个下调基因。染色体1q21上的S100家族成员在ICC中广泛上调，其中S100A11在ICC中上调程度最大。基于DE基因，结合基因本体论和京都基因和基因组百科全书分析显示局部粘附、ECM-受体相互作用和动作细胞骨架调节途径增强，表明ICC与微环境之间的沟通增强。此外，发育相关基因和发育相关通路，包括 Notch、Wnt 和 TGF-β 信号通路，在 ICC 中表现出显着的活性。综上所述，我们确定了与 HCC 或 CHC 相比，ICC 中特征性上调或下调的 DE 基因和通路。这些 DE 基因和通路为 ICC 提供了新的转录组学证据，并有助于确定新的治疗靶点。
Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are common primary liver cancers worldwide. However, the survival and prognosis of ICC are much poorer than those of HCC, indicating the different molecular characteristics and mechanisms between ICC and HCC. To identify differentially expressed (DE) genes between ICC and HCC or combined hepatocellular-cholangiocarcinoma (CHC), we performed integrated analysis of publicly available microarray Gene Expression Omnibus (GEO) datasets by MetaOmics. Three GEO datasets comprising 32 ICC biochips, 77 HCC biochips, and 34 CHC biochips were available for the data integration. We identified 7313 DE genes between ICC and HCC, including 3650 upregulated genes and 3663 downregulated genes. The S100 family members on chromosome 1q21 were extensively upregulated in ICC, and S100A11 had the greatest degree of upregulation in ICC. Based on the DE genes, combined gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed the enhanced pathways of local adhesion, ECM-receptor interaction, and regulation of action cytoskeleton, suggesting the enhanced communication between ICC and the microenvironment. Additionally, development-related genes and development-related pathways, including the Notch, Wnt, and TGF-beta signaling pathways, were shown to be active prominently in ICC. Taken together, we identified the characteristically upregulated or downregulated DE genes and pathways in ICC compared with HCC or CHC. These DE genes and pathways supply new transcriptomics evidence for ICC and could help identify new therapeutic targets.