Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea.
Clin Mol Hepatol. 2012 Dec;18(4):347-56. doi: 10.3350/cmh.2012.18.4.347. Epub 2012 Dec 21.
Hepatitis C virus (HCV) is an RNA virus that is unable to integrate into the host genome. However, its proteins interact with various host proteins and induce host responses. The oncogenic process of HCV infection is slow and insidious and probably requires multiple steps of genetic and epigenetic alterations, the activation of cellular oncogenes, the inactivation of tumor suppressor genes, and dysregulation of multiple signal transduction pathways. Stellate cells may transdifferentiate into progenitor cells and possibly be linked to the development of hepatocellular carcinoma (HCC). Viral proteins also have been implicated in several cellular signal transduction pathways that affect cell survival, proliferation, migration and transformation. Current advances in gene expression profile and selective messenger RNA analysis have improved approach to the pathogenesis of HCC. The heterogeneity of genetic events observed in HCV-related HCCs has suggested that complex mechanisms underlie malignant transformation induced by HCV infection. Considering the complexity and heterogeneity of HCCs of both etiological and genetic aspects, further molecular classification is required and an understanding of these molecular complexities may provide the opportunity for effective chemoprevention and personalized therapy for HCV-related HCC patients in the future. In this review, we summarize the current knowledge of the mechanisms of hepatocarcinogenesis induced by HCV infection.
丙型肝炎病毒（HCV）是一种 RNA 病毒，无法整合到宿主基因组中。然而，其蛋白与各种宿主蛋白相互作用，并诱导宿主反应。HCV 感染的致癌过程是缓慢而隐匿的，可能需要多个遗传和表观遗传改变、细胞癌基因的激活、肿瘤抑制基因的失活以及多个信号转导途径的失调步骤。星状细胞可能会转分化为祖细胞，并可能与肝细胞癌（HCC）的发展有关。病毒蛋白还参与了几种影响细胞存活、增殖、迁移和转化的细胞信号转导途径。目前在基因表达谱和选择性信使 RNA 分析方面的进展提高了对 HCC 发病机制的认识。在 HCV 相关 HCC 中观察到的遗传事件的异质性表明，HCV 感染诱导的恶性转化涉及复杂的机制。鉴于 HCC 在病因学和遗传学方面的复杂性和异质性，需要进一步的分子分类，并且了解这些分子复杂性可能为未来 HCV 相关 HCC 患者的有效化学预防和个体化治疗提供机会。在这篇综述中，我们总结了 HCV 感染诱导肝癌发生的机制的现有知识。
