Faculty of Medicine, Department for Infectious Diseases, University of Belgrade, 11000 Belgrade, Serbia.
University Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia.
Int J Mol Sci. 2023 Nov 7;24(22):16048. doi: 10.3390/ijms242216048.
Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) accounting for around one-third of all HCC cases. Prolonged inflammation in chronic hepatitis C (CHC), maintained through a variety of pro- and anti-inflammatory mediators, is one of the aspects of carcinogenesis, followed by mitochondrial dysfunction and oxidative stress. Immune response dysfunction including the innate and adaptive immunity also plays a role in the development, as well as in the recurrence of HCC after treatment. Some of the tumor suppressor genes inhibited by the HCV proteins are p53, p73, and retinoblastoma 1. Mutations in the telomerase reverse transcriptase promoter and the oncogene catenin beta 1 are two more important carcinogenic signaling pathways in HCC associated with HCV. Furthermore, in HCV-related HCC, numerous tumor suppressor and seven oncogenic genes are dysregulated by epigenetic changes. Epigenetic regulation of gene expression is considered as a lasting "epigenetic memory", suggesting that HCV-induced changes persist and are associated with liver carcinogenesis even after cure. Epigenetic changes and immune response dysfunction are recognized targets for potential therapy of HCC.
丙型肝炎病毒(HCV)是肝细胞癌(HCC)的主要病因,约占所有 HCC 病例的三分之一。慢性丙型肝炎(CHC)中的长期炎症通过各种促炎和抗炎介质维持,是致癌作用的一个方面,随后是线粒体功能障碍和氧化应激。包括先天免疫和适应性免疫在内的免疫应答功能障碍也在 HCC 的发展以及治疗后 HCC 的复发中起作用。一些被 HCV 蛋白抑制的肿瘤抑制基因包括 p53、p73 和视网膜母细胞瘤 1。端粒酶逆转录酶启动子和癌基因 catenin beta 1 的突变是与 HCV 相关的 HCC 中另外两个重要的致癌信号通路。此外,在 HCV 相关的 HCC 中,许多肿瘤抑制基因和七个致癌基因的表达受到表观遗传变化的调控。基因表达的表观遗传调控被认为是一种持久的“表观遗传记忆”,表明 HCV 诱导的变化持续存在,并与肝癌发生相关,即使在治愈后也是如此。表观遗传变化和免疫应答功能障碍是 HCC 潜在治疗的公认靶点。