Pathology Department, National Liver Institute, Menoufia University, Menoufia, Egypt.
Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Menofia, Egypt.
Pol J Pathol. 2022;73(2):88-98. doi: 10.5114/pjp.2022.118700.
The pathogenesis of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) differs according to whether prior treatment with interferon (IFN) vs. direct-acting antiviral agents (DAAs) was administered. Cyclo- oxygenase-2 (COX-2), yes-associated protein 1 (YAP), and transcriptional co-activator with PDZ-binding motif (TAZ) play a crucial role in hepatocarcinogenesis. However, their roles in untreated or treated HCV-related HCC development have not been clarified. Therefore, we performed an immunohistochemical study and stained tissue from 83 HCV-related HCC cases using antibodies against COX-2, YAP, and TAZ and correlated their expression with the clinicopathological characteri stics and survival data. The cases were subdivided into 3 groups based on prior HCV treatment. In the 3 groups, COX-2 was significantly higher in HCC tissue compared with adjacent non-tumour liver tissue. However, the expression of YAP/TAZ was not significantly different between HCC and adjacent non-tumour tissue. We further grouped HCC cases into YAP+/TAZ+ and YAP-/TAZ- cases. In the YAP+/TAZ+ cases, COX-2 was significantly associated with tumour size, tumour multifocality, and late pathologic stage. No significant difference was observed in COX-2 and TAZ expression as a result of IFN or DAA treatment; however, YAP was significantly higher in IFN-treated HCC. Cyclo-oxygenase-2 overexpression may play a role in late HCC development, while YAP/TAZ could play an early role in HCC progression. Sustained expression of combined YAP/TAZ could mediate the poor prognostic role of COX-2.
丙型肝炎病毒（HCV）相关肝细胞癌（HCC）的发病机制因是否先前接受干扰素（IFN）与直接作用抗病毒药物（DAA）治疗而有所不同。环氧化酶-2（COX-2）、Yes 相关蛋白 1（YAP）和含 PDZ 结合模体的转录共激活因子（TAZ）在肝癌发生中起关键作用。然而，它们在未经治疗或治疗的 HCV 相关 HCC 发展中的作用尚未阐明。因此，我们进行了免疫组织化学研究，使用针对 COX-2、YAP 和 TAZ 的抗体对 83 例 HCV 相关 HCC 病例的组织进行染色，并将其表达与临床病理特征和生存数据相关联。根据先前的 HCV 治疗情况将病例分为 3 组。在这 3 组中，HCC 组织中的 COX-2 明显高于相邻非肿瘤肝组织。然而，YAP/TAZ 的表达在 HCC 和相邻非肿瘤组织之间没有显著差异。我们进一步将 HCC 病例分为 YAP+/TAZ+和 YAP-/TAZ-病例。在 YAP+/TAZ+病例中，COX-2 与肿瘤大小、肿瘤多灶性和晚期病理分期显著相关。IFN 或 DAA 治疗并未导致 COX-2 和 TAZ 表达的显著差异；然而，IFN 治疗的 HCC 中 YAP 明显升高。COX-2 过表达可能在晚期 HCC 发展中起作用，而 YAP/TAZ 可能在 HCC 进展中起早期作用。联合 YAP/TAZ 的持续表达可能介导 COX-2 的不良预后作用。
