Objective To screen the core genes of ferroptosis and analyze the prognosis of pancreatic ductal adenocarcinoma(PDAC).Methods Based on the Gene Expression Omnibus(GEO)database,the GSE71989 data set was selected,and the differentially expressed genes(DEGs)were screened by limma package and ferroptosis data set.The Metascape database was used for enrichment analysis,the String database was used to establish a protein-protein interaction network(PPI),and the matthews correlation coefficient(MCC)algorithm was used to screen for prognostic related core genes.The Kaplan Meier plotter,R,GEPIA2 and TIMER databases were used to analyze and verify the prognosis of the selected core genes.The CMap database was used to screen potential therapeutic drugs for PDAC.Results A total of 2 038 DEGs were screened,of which 1 552 genes were up-regulated and 486 genes were down-regulated.Intersecting with the ferroptosis data set,66 common DEGs were obtained.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the enrichment pathways of ferroptosis-related genes included ferroptosis pathway,interleukin-17(IL-17)signaling pathway,chemical carcinogenesis-reactive oxygen species pathway,peroxisome proliferator-activated receptor(PPAR)signaling pathway and hypoxia inducible factor-1(HIF-1)signaling pathway.The pre-core targets:NADPH oxidase 4(NOX4),caveolin-1(CAV1),hypoxia inducible factor 1 subunit alpha(HIF1A),peroxisome proliferator activated receptor gamma(PPARG),interleukin-6(IL-6),prostaglandin-endoperoxide synthase 2(PTGS2)were obtained by MCC algorithm.The verification analysis suggested that the core genes were highly expressed genes,closely related to the overall survival rate of patients and had diagnostic value(P＜0.05).Immune infiltration showed a significant positive correlation(P＜0.05)between NOX4,HIF1A,IL-6 genes and macrophage and neutrophil infiltration levels.The NOX4,CAV1 and H1F1A genes were significantly positively correlated with CD8+and DC cell infiltration levels(P＜0.05).The selected small molecule drugs include HU-211,ispinesib,and ursolic acid,all of which have a strong correlation with PDAC.Conclusion The ferroptosis-related genes(NOX4,CAV1,HIF1A,PPARG,IL-6,PTGS2)screened based on the integrated database have a high diagnostic value for PDAC and may be a prognostic diagnostic indicator.
万方数据
维普
