Cabral Loraine Kay D, Grisetti Luca, Pratama Muhammad Yogi, Tiribelli Claudio, Pascut Devis
Fondazione Italiana Fegato-ONLUS, AREA Science Park, Basovizza, 34149 Trieste, Italy.
Doctoral School in Molecular Biomedicine, University of Trieste, 34127 Trieste, Italy.
Cancers (Basel). 2022 May 30;14(11):2700. doi: 10.3390/cancers14112700.
Hepatocellular carcinoma (HCC) is the sixth-most common type of cancer worldwide and chronic Hepatitis C virus (HCV) represents the main etiological factor in developed countries. HCV promotes hepatocarcinogenesis through persistent liver inflammation and dysregulation of cell signaling pathways. The introduction of direct-acting antivirals (DAAs) resulted in a significant improvement in the eradication of the virus, with an expected reduction of HCC incidence. However, the risk of HCC development can persist after DAA treatment. Recent studies have investigated the potential use of molecular biomarkers that predict HCC occurrence or recurrence helping the stratification of patients under surveillance. This review aimed to summarize all pre-clinical exploration of predictive biomarkers to identify DAA-treated patients at risk for HCC development. Dysregulated microRNAs, lncRNAs, histone modifications, cytokines, proteins, and sphingolipids represent various classes of HCC risk predictors identified in two different biological sources (tissue and serum). The non-invasive serum markers can provide a more accessible means to perform clinical monitoring and predict the risk of HCC. In addition, conditions like cirrhosis, predisposing to HCC, strongly correlate with most of the molecular predictors identified, supporting the value of these molecules as possible biomarkers of HCC in DAA-treated patients.
肝细胞癌（HCC）是全球第六大常见癌症类型，慢性丙型肝炎病毒（HCV）是发达国家主要的病因。HCV通过持续的肝脏炎症和细胞信号通路失调促进肝癌发生。直接作用抗病毒药物（DAAs）的引入显著提高了病毒清除率，预计肝癌发病率会降低。然而，DAA治疗后肝癌发生风险可能仍然存在。最近的研究探讨了分子生物标志物预测HCC发生或复发的潜在用途，有助于对接受监测的患者进行分层。本综述旨在总结预测生物标志物的所有临床前探索，以识别接受DAA治疗且有HCC发生风险的患者。失调的微小RNA、长链非编码RNA、组蛋白修饰、细胞因子、蛋白质和鞘脂代表了在两种不同生物来源（组织和血清）中鉴定出的各类HCC风险预测因子。非侵入性血清标志物可为临床监测和预测HCC风险提供更便捷的手段。此外，诸如肝硬化等易引发HCC的病症与大多数已鉴定的分子预测因子密切相关，支持了这些分子作为接受DAA治疗患者中HCC潜在生物标志物的价值。
