A Novel Signature Combing Cuproptosis-and Ferroptosis Related Genes in Nonalcoholic Fatty Liver Disease  

作　　者：Rou-Rou Fang Qi-Fan Yang Jing Zhao Shou-Zhu Xu 

机构地区：[1]School of Public Health,Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi,China [2]Shaanxi Key Laboratory of Acupuncture&Medicine,Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi,China

出　　处：《Chinese Medical Sciences Journal》2024年第4期261-272,共12页中国医学科学杂志（英文版）

摘　　要：Objective To identify cuproptosis-and ferroptosis-related genes involved in nonalcoholic fatty liver disease and to determine the diagnostic value of hub genes.Methods The gene expression dataset GSE89632 was retrieved from the Gene Expression Omnibus database to identify differentially expressed genes(DEGs)between the non-alcoholic steatohepatitis(NASH)group and the healthy group using the'limma'package in R software and weighted gene co-expression network analysis.Gene ontology,kyoto encyclopedia of genes and genomes pathway,and single-sample gene set enrichment analyses were performed to identify functional enrichment of DEGs.Ferroptosis-and cuproptosis-related genes were obtained from the FerrDb V2 database and available literatures,respectively.A combined signature for cuproptosis-and ferroptosis-related genes,called CRF,was constructed using the STRING database.Hub genes were identified by overlapping DEGs,WGCNA-derived key genes,and combined signature CRF genes,and validated using the GSE109836 and GSE227714 datasets and real-time quantitative polymerase chain reaction.A nomogram of NASH diagnostic model was established utilizing the'rms'package in R software based on the hub genes,and the diagnostic value of hub genes was assessed using receiver operating characteristic curve analysis.In addition,immune cell infiltration in NASH versus healthy controls was examined using the CIBERSORT algorithm.The relationships among various infiltrated immune cells were explored with Spearman's correlation analysis.Results Analysis of GSE89632 identified 236 DEGs between the NASH group and the healthy group.WGCNA highlighted 8 significant modules and 11,095 pivotal genes,of which 330 genes constituted CRF.Intersection analysis identified IL6,IL1B,JUN,NR4A1,and PTGS2 as hub genes.The hub genes were all downregulated in the NASH group,and this result was further verified by the NASH validation dataset and real-time quantitative polymerase chain reaction.Receiver operating characteristic curve analysis confirmed the diagno

关 键 词：nonalcoholic fatty liver disease cuproptosis ferroptosis bioinformatics analysis 

分 类 号：R575.5[医药卫生—消化系统]