Clinical implications and biological features of a novel postoperative recurrent HCC classification: A multi-centre study
Clinical implications and biological features of a novel postoperative recurrent HCC classification: A multi-centre study
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一种新的术后复发性 HCC 分类的临床意义和生物学特征：一项多中心研究
DOI：
10.1111/liv.15363
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发表时间：
2022-07-25
影响因子：
6.7
通讯作者：
Li, Le-Qun
中科院分区：
文献类型：
--
作者：
Qi, Lu-Nan;Ma, Liang;Li, Le-Qun
背景和目标：肝细胞癌（HCC）复发模式的多样性是患者术后生存的最重要决定因素。在精准医学时代，需要对肝癌复发进行系统的分类，以帮助预防和治疗术后肝癌复发。方法：共招募了来自四家医院的1319例复发性肝癌患者，并将其分为开发队列（n = 916）、内部验证队列（n = 225）和外部验证队列（n = 178）。结果：根据复发特点、生存率、对全身和肝功能的影响以及复发后的治疗方案，将复发分为4种亚型：I型（孤立性肝内少复发）、II型（多肝内少复发）、III型（进展性复发）和IV型（超进展性复发）。III型类似于IV型复发，表明预后极差。随后，建立了两个诺模图模型，用于III型类似于IV型复发预测，并且都表现出良好的预测性能和术前和术后策略制定的适用性。多项生物学分析显示，与IV型复发相似的III型HCC病例具有p53突变富集、CCND1扩增、高增殖/转移潜力、代谢不活跃和免疫衰竭特征。高迁移率族蛋白2（HMGA2）的过度表达增强了肝癌的高度恶性行为，通过多个分子途径，使其成为一个潜在的预后预测和治疗靶点。结论：这种“复发性肝癌分类”具有重要的潜在价值，在确定患者的手术受益，预测术后生存和指导治疗策略。多维度的生物学见解也增加了对HCC复发相关因素的了解。
Background & Aims: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine.Methods: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted.Results: Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary-intrahepatic oligorecurrence); type II (multi-intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper-progression recurrence). Type III similar to IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III similar to IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III similar to IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over-expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target.Conclusions: This 'recurrent HCC classification' has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence.