Exploring Necrotic Apoptosis-Related Key Genes Affecting Atherosclerotic Plaque Instability Based on Data Mining
Objective To explore necrotic apoptosis-related key genes affecting atherosclerotic(AS)plaque instability based on data mining.Methods Datasets including GSE163154,GSE41571 and GSE28829 were downloaded from Gene Expression Omnibus(GEO)database.The GSE163154 data set included 27 tissues with intracavitary hemorrhage(unstable AS plaque)and 16 tissues without intracavitary hemorrhage(stable AS plaque),which were used as the training set.GSE41571 dataset included 5 cases of ruptured plaque(unstable AS plaque)and 6 cases of unruptured plaque(stable AS plaque),and GSE28829 dataset included 16 cases of late plaque(unstable AS plaque)and 13 cases of early plaque(stable AS plaque),and the two data sets were combined as test sets.Necrotic apoptosis-related genes affecting AS plaque instability were identified,necrotic apoptosis-related genes affecting AS plaque instability enrichment analysis and protein-protein interaction(PPI)network analysis were performed,and candidate core genes were screened,and then core genes were screened by principal component analysis and receiver operating characteristics(ROC)curve.Results A total of 7 652 differentially expressed genes(DEGs)were screened from the GSE163154 dataset,and 75 necrotic apoptosis-related genes affecting AS plaque instability were obtained.Gene ontology(GO)functional enrichment analysis showed that in terms of biological process(BP),necrotic apoptosis-related genes affecting AS plaque instability were mainly involved in cytokine-mediated signaling pathway;in terms of cellular component(CC),necrotic apoptosis-related genes affecting AS plaque instability were mainly involved in autophagosome;in terms of molecular function(MF),necrotic apoptosis-related genes affecting AS plaque instability were mainly involved in cytokine receptor binding.The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis showed that necrotic apoptosis-related genes affecting AS plaque instability may involve lipid and AS,Janus kinase(JAK)-signal transducer and activator of transcription(STAT)signaling pathway,NF-κB signaling pathway,tumor necrosis factor(TNF)signaling pathway,and IL-17 signaling pathway.The results of PPI network analysis showed that the candidate core genes were TNF,IL1B,STAT1,TLR4,IFNG,STAT3,JAK2,IFNAR1,IFNGR1,TYK2,STAT2,STAT4,STAT5A,STAT5B,IL1A,IRF9,BCL2,CASP1,TNFRSF1A and CFLAR.The results of principal component analysis showed that unstable AS plaque tissue in the test set could be distinguished from stable AS plaque tissue,indicating that the data were reliable.ROC curve analysis results showed that the AUC of JAK2,IFNGR1,TYK2,STAT2,STAT5A and CASP1 in predicting unstable AS plaques in the test set was 0.857,0.742,0.799,0.719,0.709,and 0.902,respectively,which were all greater than 0.70,and they were taken as the core genes.Conclusion JAK2,IFNGR1,TYK2,STAT2,STAT5A and CASP1 are the key genes related to necrotic apoptosis that affect the instability of AS plaques.
万方数据
维普
