Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C
Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C
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DOI：
10.1002/hep.21383
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发表时间：
2006-11-01
期刊：
影响因子：
13.5
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
--
作者：
Honda, Masao;Yamashita, Taro;Kaneko, Shuichi
慢性乙型肝炎（CH-B）和慢性丙型肝炎（CH-C）的临床表现不同。我们之前报道了CH-B或CH-Q感染肝组织的基因表达谱差异，然而，每种情况下的信号通路尚未明确。利用从肝脏基因表达序列分析（SAGE）文库的256,550个标签中选择的9614个克隆组成的新构建的cDNA芯片，我们比较了24例CH-B患者和23例CH-C患者的肝组织基因表达谱。采用激光捕获显微解剖技术，从16例患者的肝小叶中分离肝细胞，从门静脉区分离浸润性淋巴样细胞，进行基因表达分析。此外，利用SAGE文库分析了CH-B和CH-C的综合基因网络。监督学习和非监督学习方法显示，基因表达与感染病毒的相关性大于任何其他临床参数，如组织学分期和疾病活动性。促凋亡反应和DNA修复反应在CH-B中占主导地位，p53和14-3-3相互作用基因在其中起重要作用。相反，炎症和抗凋亡表型在CH-C中占主导地位。这些差异会在CH-B和CH-C中引起不同的致癌因子。总之，我们描述了CH-B或CH-C患者肝脏中诱导的不同信号通路。该结果可能有助于指导治疗策略，以防止CH-B和CH-C的肝细胞癌的发展。
The clinical manifestations of chronic hepatitis B (CH-B) and chronic hepatitis C (CH-C) are different. We previously reported differences in the gene expression profiles of liver tissue infected with CH-B or CH-Q however, the signaling pathways underlying each condition have yet to be clarified. Using a newly constructed cDNA microarray consisting of 9614 clones selected from 256,550 tags of hepatic serial analysis of gene expression (SAGE) libraries, we compared the gene expression profiles of liver tissue from 24 CH-B patients with those of 23 CH-C patients. Laser capture microdissection was used to isolate hepatocytes from liver lobules and infiltrating lymphoid cells from the portal area, from 16 patients, for gene expression analysis. Furthermore, the comprehensive gene network was analyzed using SAGE libraries of CH-B and CH-C. Supervised and nonsupervised learning methods revealed that gene expression was correlated more with the infecting virus than any other clinical parameters such as histological stage and disease activity. Pro-apoptotic and DNA repair responses were predominant in CH-B with p53 and 14-3-3 interacting genes having an important role. In contrast, inflammatory and anti-apoptotic phenotypes were predominant in CH-C. These differences would evoke different oncogenic factors in CH-B and CH-C. In conclusion, we describe the different signaling pathways induced in the livers of patients with CH-B or CH-C. The results might be useful in guiding therapeutic strategies to prevent the development of hepatocellular carcinoma in cases of CH-B and CH-C.