Xue Miao, Wu Yanqin, Fan Wenzhe, Guo Jian, Wei Jialiang, Wang Hongyu, Tan Jizhou, Wang Yu, Yao Wang, Zhao Yue, Li Jiaping
Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Cancer Res Treat. 2020 Jul;52(3):925-937. doi: 10.4143/crt.2019.533. Epub 2020 Mar 30.
This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)-related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE).
From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA).
Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness.
Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.
本研究旨在探讨接受经动脉化疗栓塞术（TACE）的乙型肝炎病毒（HBV）相关晚期肝细胞癌（HCC）患者的临床病理特征及突变图谱。
2017年1月至2018年12月，38例新诊断为HBV相关晚期HCC的患者纳入最终分析。收集他们在TACE治疗前的病理组织及相应血液样本进行全外显子测序。在连续两次使用TACE后1 - 3个月评估TACE反应。在二元逻辑回归模型中通过单因素和多因素分析来分析预测因素。使用基因集富集分析（GSEA）获得所有驱动基因相关通路的富集情况。
38例患者中，23例（60.5%）出现TACE失败/难治。TACE失败/难治的患者TP53突变频率高于对照组（p = 0.020）。单因素和多因素分析显示，在HBV相关晚期HCC中，仅血管侵犯和TP53突变与TACE失败/难治显著相关。在16例无血管侵犯的患者中，8例（50.0%）有TP53突变，且TP53突变与TACE失败/难治相关（p = 0.041）。此外，GSEA显示TP53突变诱导的丝裂原活化蛋白激酶和凋亡通路可能与TACE失败/难治相关。
我们的研究表明，TP53突变与TACE疗效独立相关，可能通过丝裂原活化蛋白激酶和凋亡通路起作用。这些发现可能为区分在HBV相关晚期HCC中哪些患者将特别受益于TACE，哪些患者需要更个性化的治疗方案和严格监测提供证据。
