RESUMO
BACKGROUND AND AIMS: This study aimed to explore potential hub genes and pathways of plaque vulnerability and to investigate possible therapeutic targets for acute coronary syndrome (ACS). METHODS AND RESULTS: Four microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene coexpression networks (WGCNA) and immune cell inï¬ltration analysis (IIA) were used to identify the genes for plaque vulnerability. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology, Gene Ontology annotation and protein-protein interaction (PPI) network analyses were performed to explore the hub genes. Random forest and artiï¬cial neural networks were constructed for validation. Furthermore, the CMap and Herb databases were employed to explore possible therapeutic targets. A total of 168 DEGs with an adjusted P < 0.05 and approximately 1974 IIA genes were identified in GSE62646. Three modules were detected and associated with CAD-Class, including 891 genes that can be found in GSE90074. After removing duplicates, 114 hub genes were used for functional analysis. GO functions identified 157 items, and 6 pathways were enriched for the KEGG pathway at adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). Random forest and artificial neural network models were built based on the GSE48060 and GSE34822 datasets, respectively, to validate the previous hub genes. Five genes (GZMA, GZMB, KLRB1, KLRD1 and TRPM6) were selected, and only two of them (GZMA and GZMB) were screened as therapeutic targets in the CMap and Herb databases. CONCLUSION: We performed a comprehensive analysis and validated GZMA and GZMB as a target for plaque vulnerability, which provides a therapeutic strategy for the prevention of ACS. However, whether it can be used as a predictor in blood samples requires further experimental verification.
Assuntos
Biologia Computacional , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Placa Aterosclerótica , Mapas de Interação de Proteínas , Humanos , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/terapia , Redes Neurais de Computação , Ruptura Espontânea , Predisposição Genética para Doença , Transdução de Sinais , Regulação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Transcriptoma , Terapia de Alvo Molecular , Marcadores Genéticos , Fenótipo , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/terapiaRESUMO
The primary and secondary tuberculosis features two completely different pathogenesis.At present,the pathogenesis of primary tuberculosis has been clear,whereas that of secondary tuberculosis remains unclear.In order to decipher the mechanism of secondary infection of
