Zhang Shangdi, Du Kewei, Gao Shan, Liu Zejing, Chen Linmei, Wu Xue, Li Linjing
Laboratory Medicine Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China.
Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China.
Hum Genet. 2025 May 27. doi: 10.1007/s00439-025-02753-x.
Hepatocellular carcinoma (HCC) is a primary liver malignancy with a dismal prognosis. This study established and validated a prognostic model based on antigen-processing and presenting machinery (APM)-related genes through Mendelian randomization and publicly available datasets. Systematic analysis revealed CXCL5, SGPP2, and GLP1R as critical prognostic biomarkers, which were subsequently integrated into a risk model. The model demonstrated significant associations with pathways linked to bile acid, fatty acid, and amino acid metabolism, alongside variations in immune cell infiltration and genomic mutations, including TTN, TP53, and MUC16. Patient stratification into high- and low-risk groups indicated that low-risk individuals exhibited reduced immune infiltration, potentially correlating with enhanced immunotherapy sensitivity. These findings offer a robust gene signature for HCC prognosis and a framework for evaluating responses to immunotherapy.
肝细胞癌（HCC）是一种预后不佳的原发性肝脏恶性肿瘤。本研究通过孟德尔随机化和公开可用数据集，建立并验证了一种基于抗原加工和呈递机制（APM）相关基因的预后模型。系统分析显示CXCL5、SGPP2和GLP1R为关键的预后生物标志物，随后将其整合到一个风险模型中。该模型显示与胆汁酸、脂肪酸和氨基酸代谢相关的通路存在显著关联，同时免疫细胞浸润和基因组突变（包括TTN、TP53和MUC16）也存在差异。将患者分层为高风险和低风险组表明，低风险个体的免疫浸润减少，这可能与免疫治疗敏感性增强相关。这些发现为HCC预后提供了一个强大的基因特征，并为评估免疫治疗反应提供了一个框架。
