基于TCGA胰腺癌数据集识别胰腺癌相关糖尿病特征基因

Identification of the feature genes of pancreatic cancer-associated diabetes mellitus based on the pancreatic cancer cohort from TGCA

目的:探讨胰腺癌相关糖尿病(PCDM)的基因特征,筛选潜在的分子标志物。方法:收集来自癌症基因组图谱(TCGA)-胰腺癌(PC)数据集的临床数据,根据PC确诊前2年内是否诊断糖尿病,将患者分为PCDM组(11例)和PC组(109例)。提取TCGA-PC数据集mRNA的芯片表达谱数据,通过R软件"limma"程序包进行两组基因差异表达分析,以"|log 2(fold change)|>2且P<0.05"为条件筛选差异基因(DEGs),并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,最后通过STRING数据库构建蛋白相互作用(PPI)网络,通过Cytoscape软件MCODE模块筛选枢纽基因。结果:TCGA-PC数据集mRNA基因差异分析显示,20531个基因中47个在PCDM组高表达,60个低表达。GO分析显示107个DEGs在生物学功能方面主要参与正向调节细胞分泌功能(基因数=9,P<0.01),在分子功能方面主要集中于受体功能调节(基因数=10,P<0.01),在细胞组分方面主要与细胞质微管腔内成分相关(基因数=8,P<0.01)。KEGG通路富集分析显示,107个DEGs可能通过细胞因子相互作用(基因数=8,P<0.01)影响PCDM。PPI网络分析显示,GNG8、CNR2、GALR2、CXCL13、NPY2R可能是PCDM相关的枢纽基因。结论:PCDM与PC在细胞分泌功能、受体功能、细胞质微管成分及细胞因子相互作用方面存在基因差异。GNG8、CNR2、GALR2、CXCL13、NPY2R可能成为PCDM的潜在分子标志物。

Objective To investigate the genetic characteristics of pancreatic cancer-associated diabetes mellitus(PCDM)and screen out the possible molecular markers for PCDM.Methods The clinical data of pancreatic cancer(PC)cohort from The Cancer Genome Atlas(TCGA)were selected and collected,and the patients were divided into PCDM(n=11)and PC groups(n=109)according to whether the patients were diagnosed as diabetes within 2 years of PC diagnosis.Then,the mRNA microarray data of genome expression were extracted from TCGA PC cohort,and the differentially expressed genes(DEGs)were screened out by the"limma"package of R software based on(|log2 fold change|>2 and P<0.05).The functions of DEGs were revealed with gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Finally,a protein-protein interaction(PPI)network was constructed with the STRING database,and the hub genes were identified by the molecular complex detection(MCODE)module of Cytoscape software.Results The analysis showed that among 20531 genes,47 genes were significantly upregulated,and 60 genes were significantly downregulated in the PCDM group.GO analyses revealed that 107 DEGs were mainly involved in the positive regulation of secretory function in terms of biological function(gene number=9,P<0.01);in the regulation of receptor function of molecular function(gene number=10,P<0.01);and in the intracavitary components of cytoplasmic microtubules of cellular components(gene number=8,P<0.01).The results of KEGG pathway enrichments revealed that DEGs mainly affected PCDM via cytokine interactions(gene number=8,P<0.01).Finally,five hub genes,including GNG8,CNR2,GALR2,CXCL13,and NPY2R,were identified for PCDM in PPI network analysis.Conclusions The feature genes of PCDM are mainly different from PC in terms of secretion function,receptor function,cytoplasmic microtubule composition,and cytokine interaction.Five genes including GNG8,CNR2,GALR2,CXCL13,and NPY2R may become potential molecular markers for PCDM.