Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China.
Department of Pathology, The First Hospital of Jilin University, Changchun, Jilin, China.
Gut. 2023 Nov;72(11):2149-2163. doi: 10.1136/gutjnl-2023-330461. Epub 2023 Aug 7.
Selecting interventions for patients with solitary hepatocellular carcinoma (HCC) remains a challenge. Despite gross classification being proposed as a potential prognostic predictor, its widespread use has been restricted due to inadequate studies with sufficient patient numbers and the lack of established mechanisms. We sought to investigate the prognostic impacts on patients with HCC of different gross subtypes and assess their corresponding molecular landscapes.
A prospective cohort of 400 patients who underwent hepatic resection for solitary HCC was reviewed and analysed and gross classification was assessed. Multiomics analyses were performed on tumours and non-tumour tissues from 49 patients to investigate the mechanisms underlying gross classification. Inverse probability of treatment weight (IPTW) was used to control for confounding factors.
Overall 3-year survival rates varied significantly among the four gross subtypes (type I: 91%, type II: 80%, type III: 74.6%, type IV: 38.8%). Type IV was found to be independently associated with poor prognosis in both the entire cohort and the IPTW cohort. The four gross subtypes exhibited three distinct transcriptional modules. Particularly, type IV tumours exhibited increased angiogenesis and immune score as well as decreased metabolic pathways, together with highest frequency of TP53 mutations. Patients with type IV HCC may benefit from adjuvant intra-arterial therapy other than the other three subtypes. Accordingly, a modified trichotomous margin morphological gross classification was established.
Different gross types of HCC showed significantly different prognosis and molecular characteristics. Gross classification may aid in development of precise individualised diagnosis and treatment strategies for HCC.
选择单个肝细胞癌（HCC）患者的干预措施仍然具有挑战性。尽管大体分类被提出作为一种有潜力的预后预测指标，但由于缺乏足够数量的患者的充分研究以及缺乏既定机制，其广泛应用受到限制。我们旨在研究不同大体类型对 HCC 患者的预后影响，并评估其相应的分子特征。
回顾性分析了 400 例接受肝切除术治疗的单个 HCC 患者的前瞻性队列，并进行了大体分类评估。对 49 例患者的肿瘤和非肿瘤组织进行了多组学分析，以研究大体分类的潜在机制。采用逆概率治疗加权（IPTW）来控制混杂因素。
四种大体类型的总体 3 年生存率差异显著（Ⅰ型：91%，Ⅱ型：80%，Ⅲ型：74.6%，Ⅳ型：38.8%）。在整个队列和 IPTW 队列中，均发现Ⅳ型与预后不良独立相关。四种大体类型表现出三个不同的转录模块。特别是，Ⅳ型肿瘤表现出增加的血管生成和免疫评分，以及减少的代谢途径，同时具有最高频率的 TP53 突变。与其他三种类型相比，Ⅳ型 HCC 患者可能受益于辅助动脉内治疗。因此，建立了一种改良的三分类边缘形态大体分类。
不同的 HCC 大体类型表现出明显不同的预后和分子特征。大体分类可能有助于为 HCC 制定精确的个体化诊断和治疗策略。
