诊断学理论与实践2025，Vol.24Issue(1)：27-34,8.DOI:10.16150/j.1671-2870.2025.01.005
细胞失巢相关基因PDK4与2型糖尿病发病相关——基于生物信息的研究
Anoikis-related gene PDK4 and pathogenesis of type 2 diabetes mellitus:A bioinformatics-based study
摘要
Abstract
Objective To identify anoikis-related genes and immune infiltration characteristics in pancreas islet tissues involved in the pathogenesis of type 2 diabetes mellitus(T2DM)using bioinformatic analysis.Methods The dataset GSE76894 was downloaded from the Gene Expression Omnibus(GEO)database as the training set.Diffe-rential gene expression analysis was conducted on T2DM and non-diabetic islet tissues within the training set,and intersected with the anoikis-related gene set to obtain anoikis-related differentially expressed genes(DEGs).Subse-quently,key genes were identified using the random forest(RF)and least absolute shrinkage and selection operator(LASSO)algorithms.Receiver operating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was calculated to evaluate the association strength between the expression levels of the identified key genes in pan-creas islet tissues and T2DM,followed by validation in the GSE76895 dataset.Protein-protein interaction(PPI)net-work analysis and gene ontology(GO)enrichment analysis were then performed on the identified key genes.The immune infiltration analysis was conducted using the CIBERSORT algorithm.Results Differential analysis identified 8 anoikis-related DEGs,with 6 upregulated and 2 downregulated genes.Subsequent application of two machine lear-ning algorithms identified 4 key genes:PDK4,BMF,ITGB1,and SNAI2.ROC analysis showed that in the validation set(GSE76895),only PDK4 expression had strong discriminatory power(AUC=0.721),indicating a significant asso-ciation with T2DM.Enrichment analysis demonstrated that these key genes were primarily enriched in terms related to integrin-mediated cell adhesion,regulation of lipid biosynthetic processes,integrin complex,and glial cell protru-sions.Immune infiltration analysis indicated differential expression of various immune cells in the pancreas islet tis-sues of T2DM and healthy individuals.Furthermore,PDK4 expression was negatively correlated with that of M0 macro-phages.Conclusions PDK4 is downregulated in T2DM islet tissues and negatively correlated with M0 macrophage expression levels,suggesting that the expression of PDK4 is related to the T2DM pathogenesis caused by immune dys-regulation to some extent.关键词
2型糖尿病/失巢凋亡/生物信息学Key words
Type 2 diabetes mellitus/Anoikis/Bioinformatics分类
医药卫生引用本文复制引用
张珂,张唯一,孙海天,曹铭峰,张新焕..细胞失巢相关基因PDK4与2型糖尿病发病相关——基于生物信息的研究[J].诊断学理论与实践,2025,24(1):27-34,8.基金项目
山东省医药卫生科技项目(202303060522) （202303060522）
