Gene expression profiling of hepatitis B- and hepatitis C-related hepatocellular carcinoma using graphical Gaussian modeling
Gene expression profiling of hepatitis B- and hepatitis C-related hepatocellular carcinoma using graphical Gaussian modeling
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DOI：
10.1016/j.ygeno.2013.02.007
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发表时间：
2013-04-01
期刊：
影响因子：
4.4
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
--
作者：
Ueda, Teruyuki;Honda, Masao;Kaneko, Shuichi
背景和目标：肝细胞癌（HCC）和背景肝脏的基因表达谱已被广泛研究;然而，不同病变的基因表达谱之间的关系尚未评估。我们检测了34例HCC标本的表达谱，（17例B型肝炎病毒[HBV]相关和17例丙型肝炎病毒[HCV]相关）和71例非肿瘤肝脏标本（36例慢性B型肝炎[CH-B]和35例慢性丙型肝炎[CH-C]）使用由肝脏优势基因组成的内部cDNA微阵列。结果：在CH-B相关的HCC中，血管内皮生长因子家族信号传导和调节T细胞分化、凋亡、存活以及发育相关基因的表达上调。在CH-C相关的HCC中，外胚层发育和细胞增殖、wnt受体信号传导、细胞粘附和防御反应基因的表达也上调。许多代谢相关基因在CH-B和CH-C相关的HCC中表达下调。肝癌和非肿瘤病变的GGM分析显示，DNA损伤反应基因与非肿瘤病变中的AP 1信号相关，AP 1信号介导CH-B相关肝癌中许多基因的表达。相反，信号转导和转录激活因子1和磷酸酶和张力蛋白同源物与早期生长反应蛋白1信号在非肿瘤病变，这可能促进血管生成，纤维化，和肿瘤发生在CH-C相关的HCC.Conclusions：基因表达谱的HCC和非肿瘤病变揭示了基因表达的易感性变化在HCC。这种方法具有早期诊断和可能的预防HCC的潜力。(C)2013 Elsevier Inc. All rights reserved.
Background & aims: Gene expression profiling of hepatocellular carcinoma (HCC) and background liver has been studied extensively; however, the relationship between the gene expression profiles of different lesions has not been assessed.Methods: We examined the expression profiles of 34 HCC specimens (17 hepatitis B virus [HBV]-related and 17 hepatitis C virus [HCV]-related) and 71 non-tumor liver specimens (36 chronic hepatitis B [CH-B] and 35 chronic hepatitis C [CH-C]) using an in-house cDNA microarray consisting of liver-predominant genes. Graphical Gaussian modeling (GGM) was applied to elucidate the interactions of gene clusters among the HCC and non-tumor lesions.Results: In CH-B-related HCC, the expression of vascular endothelial growth factor-family signaling and regulation of T cell differentiation, apoptosis, and survival, as well as development-related genes was up-regulated. In CH-C-related HCC, the expression of ectodermal development and cell proliferation, wnt receptor signaling, cell adhesion, and defense response genes was also up-regulated. Many of the metabolism-related genes were down-regulated in both CH-B- and CH-C-related HCC. GGM analysis of the HCC and non-tumor lesions revealed that DNA damage response genes were associated with AP1 signaling in non-tumor lesions, which mediates the expression of many genes in CH-B-related HCC. In contrast, signal transducer and activator of transcription 1 and phosphatase and tensin homolog were associated with early growth response protein 1 signaling in non-tumor lesions, which potentially promotes angiogenesis, fibrogenesis, and tumorigenesis in CH-C-related HCC.Conclusions: Gene expression profiling of HCC and non-tumor lesions revealed the predisposing changes of gene expression in HCC. This approach has potential for the early diagnosis and possible prevention of HCC. (C) 2013 Elsevier Inc. All rights reserved.