南京中医药大学学报2026，Vol.42Issue(4)：583-595,13.DOI:10.14148/j.issn.1672-0482.2026.0583
基于多组学分析探索胃瘤安合剂调控成纤维细胞亚群改善胃癌免疫微环境的机制
Multi-Omics Analysis of Wei-Liu-An Mixture in Modulating Fibroblast Subpopulations to Improve the Immune Microenvironment in Gastric Cancer
摘要
Abstract
OBJECTIVE This study aims to identify immune-related subtypes,prognostic biomarkers and potential therapeutic targets in gastric cancer(GC)through integrative multi-omics analysis,with a particular focus on the immunoregulatory mechanisms mediated by the active components of the traditional Chinese herbal formula Wei-Liu-An Mixture(Wei-Liu-An-He-Ji,abbreviated as Wei-Liu-An).METHODS Based on immune infiltration profiles,unsupervised clustering was performed to stratify GC patients into three immune phenotypes:an immune-desert subtype(Cluster 1),an immune-excluded subtype(Cluster 2)and an immune-inflamed subtype(Cluster 3).Differentially expressed genes(DEGs)among immune subtypes were identified and intersected with metabolite-related targets of Wei-Liu-An Mixture obtained by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).Single-cell RNA sequencing(scRNA-seq)data were leveraged to delineate the cell-type-specific expression pat-terns and putative localization features of prognostic genes across distinct tumour immune microenvironment(TIME)compartments,with particular emphasis on functional enrichment analyses of crystallin alpha B(CRYAB)-positive fibroblasts.Finally,we developed an immune-inflamed subtype-derived 9-gene prognostic risk score model,termed IIP-9GS(Immune-Inflamed phenotype-derived 9-Gene Signature Risk Score),and externally validated its predictive performance for survival risk stratification in two independent GC co-horts.RESULTS The IIP-9GS prognostic risk score model effectively stratified patients with GC into high-and low-risk groups,demonstrating robust and stable discriminative performance across cohorts.Among the signature genes,interferon regulatory factor 1(IRF1)and interferon-gamma(IFNG)were identified as potential targets of Wei-Liu-An,and their high expression was significantly as-sociated with favorable prognosis.In contrast,CRYAB was downregulated in the immune-inflamed Cluster 3,whereas previous analy-ses indicated that its high expression correlated with poor survival,suggesting that CRYAB may represent a key high-risk gene in GC.Notably,CRYAB was highly enriched in fibroblasts,smooth muscle cells and endothelial cells,implying that it may exert complex bio-logical effects by modulating the stromal compartment of the TIME.CONCLUSION The study performs multi-omics integrative bio-informatics analyses based on immune infiltration characteristics in gastric cancer(GC)and establishes the IIP-9GS prognostic risk score model.At the single-cell level,it suggests that CRYAB⁺ fibroblasts may represent a pivotal stromal regulatory node within the TIME.Integrating target prediction results for the active constituents of the Wei-Liu-An,we propose that Wei-Liu-An may contribute to TIME remodeling by modulating immune-related pathways and stromal cell states,thereby alleviating immunosuppression and miti-gating stroma-associated resistance.Collectively,CRYAB and its associated fibroblast subpopulations may serve as potential prognos-tic biomarkers and therapeutic targets for overcoming immunosuppression and stroma-driven resistance,providing new clues and a theoretical basis for individualized integrative treatment strategies in GC.关键词
胃癌/胃瘤安合剂/肿瘤免疫微环境/传统中医治疗/免疫激活表型/预后基因Key words
gastric cancer/Wei-Liu-An Mixture/tumour immune microenvironment/traditional Chinese medicine treatment/immune-inflamed phenotype/prognostic genes分类
医药卫生引用本文复制引用
朱崇薇,王济霞,冉艳文,张照阳,林建秀,王晓露,田赟..基于多组学分析探索胃瘤安合剂调控成纤维细胞亚群改善胃癌免疫微环境的机制[J].南京中医药大学学报,2026,42(4):583-595,13.基金项目
江苏省中医院科研基金(kgr0255) （kgr0255）
南京市科技发展计划项目(202511014) （202511014）
江苏省中医药科学技术发展项目(MS2023015) （MS2023015）
南京中医药大学大学生创新计划项目(SJCX24_1004) （SJCX24_1004）
