南方医科大学学报2026，Vol.46Issue(5)：977-993,17.DOI:10.12122/j.issn.1673-4254.2026.05.02
多组学整合揭示结直肠癌中的免疫-代谢异质性:针对ANGPTL4/FABP4/RBP7的预后模型及治疗策略
Multi-omics integration deciphers immune-metabolic heterogeneity in colorectal cancer:a prognostic model and therapeutic strategies targeting ANGPTL4/FABP4/RBP7
摘要
Abstract
Objective To explore the heterogeneity of tumor immune microenvironment(TIME)in colorectal cancer(CRC)and the resultant treatment resistance and develop a prognostic model for predicting the treatment outcomes of CRC.Methods The multi-omics data including transcriptomic,somatic mutation and single-cell RNA sequencing data of a total of 1136 CRC samples from a TCGA cohort(n=568)and a GEO cohort(n=568)were integrated.The TCGA cohort was divided into Immunity_High and Immunity_Low subtypes by single-sample gene set enrichment analysis(ssGSEA)and t-SNE algorithm.A prognostic model was constructed using univariate Cox regression combined with LASSO-Cox regression,and the functions of the core genes including ANGPTL4,FABP4 and RBP7 were verified by single cell RNA-seq,molecular docking,kinetic simulations and qPCR/IHC experiments.Results The Immunity_High subtype of CRC was enriched with CD8+T cells and had significantly longer patient survival,while the Immunity_Low subtype was characterized by M0 macrophage infiltration.The prognostic model constructed based on 12 genes including ANGPTL4,FABP4 and RBP7 showed good predictive performance,with the AUC of 3-year survival rate reaching 0.765,an overall AUC of 0.76 in the TCGA cohort,and an overall AUC of 0.70 in the GEO cohort.Mechanistically,ANGPTL4 regulated macrophage polarization,FABP4 mediated fibroblast reprogramming,and RBP7 up-regulated PD-L1 expression.Molecular docking and kinetic simulations confirmed stable binding of retinoic acid and rosiglitazone to the core targets with the minimum binding energy of-8.3 kcal/mol.Conclusion The constructed prognostic model and the identified potential therapeutic targets provide new strategies to address immune therapy resistance for CRC.关键词
结直肠癌/多组学整合/免疫代谢异质性/预后模型/ANGPTL4/FABP4/RBP7Key words
colorectal cancer/multi-omics integration/immune-metabolic heterogeneity/prognostic model/ANGPTL4/FABP4/RBP7引用本文复制引用
丁宁,张英杰,彭天书,莫黎,胡响当,杨宗亮,肖佑,付肖冰,赵建政,李磊磊..多组学整合揭示结直肠癌中的免疫-代谢异质性:针对ANGPTL4/FABP4/RBP7的预后模型及治疗策略[J].南方医科大学学报,2026,46(5):977-993,17.基金项目
中国博士后面上项目(2025M773937) （2025M773937）
国家资助博士后研究人员计划(GZC20230773) （GZC20230773）
湖南省教育厅重点课题(24A0262) （24A0262）
湖南中医药大学校级课题(2022XYLH026) （2022XYLH026）
湖南省中医药管理局科研基金项目(B2024094) （B2024094）
湖南中医药大学科研基金项目(2022XYLH038) （2022XYLH038）
