西安交通大学学报（医学版）2026，Vol.47Issue(2)：257-268,12.DOI:10.7652/jdyxb202602009
非酒精性脂肪性肝病的转录组学特征及关键分子解析
Bioinformatics analysis of transcriptomic signatures and key molecules in non-alcoholic fatty liver disease
摘要
Abstract
Objective Non-alcoholic fatty liver disease(NAFLD)is a common chronic liver disorder worldwide,with non-alcoholic steatohepatitis(NASH)carrying a high risk of progression to fibrosis,cirrhosis,and hepatocellular carcinoma.This study aimed to identify key molecular events underlying the transition from non-alcoholic fatty liver(NAFL)to NASH by integrating multi-cohort transcriptomic data,thereby providing potential early biomarkers and therapeutic targets.Methods Four liver tissue RNA-seq datasets from the GEO database(total n=293)were collected and integratd.After quality control and batch correction,286 high-quality samples were retained(HC=46,NAFL=70,NASH=170).Differentially expressed genes(DEGs)were identified using three analytical pipelines(edgeR,limma-voom,and DESeq2).Functional enrichment was performed through GSEA,GO,and KEGG analyses,followed by consensus pathway screening and validation of pathway activity using single-sample GSEA(ssGSEA).Results NAFL showed mild disturbances in metabolic homeostasis and low-grade inflammation.In contrast,NASH displayed pronounced activation of pathways related to inflammation,immune response,cell cycle regulation,and extracellular matrix(ECM)remodeling.Comparison of NASH and NAFL highlighted pronounced cell cycle dysregulation,enhanced inflammation,and ECM-related changes.ssGSEA verified progressive activation of E2F targets,G2/M checkpoint,and TNF-α/NF-κB signaling along the disease spectrum.Conclusion The progression from NAFL to NASH involves a gradual shift from metabolic imbalance to inflammation,cell cycle dysregulation,and ECM remodeling.This study delineates the transcriptomic landscape of NAFLD progression and provides a valuable resource for mechanistic insights and identification of potential therapeutic targets.关键词
非酒精性脂肪性肝病(NAFLD)/非酒精性脂肪性肝炎(NASH)/转录组学/差异表达基因(DEGs)Key words
non-alcoholic fatty liver disease(NAFLD)/non-alcoholic steatohepatitis(NASH)/transcriptomics/differentially expressed gene(DEGs)分类
医药卫生引用本文复制引用
高姝雅,姚雨璐,田垚,管培中,申佳琦,李生斌,成诚..非酒精性脂肪性肝病的转录组学特征及关键分子解析[J].西安交通大学学报（医学版）,2026,47(2):257-268,12.基金项目
西安交通大学横向项目(No.HXDSH20231721),国家级大学生创新训练项目(No.202510698046)Supported by Xi'an Jiaotong University Crosswise Project(No.HXDSH20231721)and the National College Students'Innovation and Entrepreneurship Training Program(No.202510698046) （No.HXDSH20231721）
