选取对于单发肝细胞癌（HCC）患者的治疗干预仍然是一个挑战。尽管毛病分类被提议作为潜在的预后预测因子，但由于研究样本数量不足和缺乏确立的机制，其普及运用受到限制。我们旨在研究不同毛病亚型对HCC患者预后的影响，并评估它们相应的分子景观。回顾并分析了400名行肝切除术治疗单发HCC的患者的前瞻性队列，并评估了毛病分类。对49名患者的肿瘤和非肿瘤组织进行了多组学分析，以研究毛病分类背后的机制。使用倒数概率权重（IPTW）来控制混杂因素。总体而言，四种毛病亚型的3年生存率存在显著差异（I型：91%，II型：80%，III型：74.6%，IV型：38.8%）。在整个队列和IPTW队列中，发现IV型与不良预后独立相关。四种毛病亚型显示出三个明显的转录模块。特别是，IV型肿瘤表现出增加的血管生成和免疫分数，以及代谢途径的降低，同时伴有最高频率的TP53突变。IV型HCC患者可能从除其他三个亚型外的辅助肝动脉治疗中获益。因此，建立了经修饰的三分界面形态毛病分类。不同毛病类型的HCC显示出显著不同的预后和分子特征。毛病分类可能有助于HCC的精确个体化诊断和治疗策略的发展。 © 作者（或其雇主）2023。在CC BY-NC许可下允许再次使用。不允许商业再利用。BMJ出版。

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.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.