Identification of an Immune-Related Gene Diagnostic Model and Potential Drugs in Sepsis Using Bioinformatics and Pharmacogenomics Approaches.
WGCNA
diagnosis
drug target
immune infiltration
sepsis
Journal
Infection and drug resistance
ISSN: 1178-6973
Titre abrégé: Infect Drug Resist
Pays: New Zealand
ID NLM: 101550216
Informations de publication
Date de publication:
2023
2023
Historique:
received:
21
04
2023
accepted:
17
08
2023
medline:
4
9
2023
pubmed:
4
9
2023
entrez:
4
9
2023
Statut:
epublish
Résumé
Sepsis is an organ dysfunction with high mortality. Early identification, diagnosis, and effective treatment of sepsis are beneficial to the survival of patients. This study aimed to find potential diagnosis and immune-related genes, and drug targets, which could provide novel diagnostic and therapeutic markers for sepsis. The GSE69063, GSE154918 and GSE28750 datasets were integrated to evaluate immune infiltration and identify differentially expressed genes (DEGs) and immune-related genes. Weighted gene co-expression network analysis (WGCNA) was applied to find the hub module related to immune score and sepsis. Immune-related key genes were screened out by taking interaction of DEGs, immune-related genes, and genes in hub module. Protein-protein interaction (PPI) analysis was used to further screen immune-related hub genes, followed by construction of a diagnostic model based on immune-related hub genes. Functional analysis and drug prediction of immune-related hub genes were, respectively, performed by David software and DGIdb database, followed by expression validation by reverse transcriptase polymerase chain reaction (RT-PCR). Totally, 93 immune-related key genes were identified between 561 DEGs, 1793 immune-related genes and 12,459 genes in the hub module of WGCNA. Through PPI analysis, a total of 5 diagnose and immune-related hub genes were further obtained, including IL7R, IL10, CD40LG, CD28 and LCN2. Relationship pairs between these 5 genes and immune cell were identified, including LCN2/IL7R/CD28-activated dendritic cell and IL10-immature B cell. Based on pharmacogenomics, 17 candidate drugs might interact with IL 10, including CYCLOSPORINE. Six candidate drugs might interact with CD28 and 11 with CD40LG, CD40LG and CD28 were drug targets of ALDESLEUKIN. Four significantly enriched signaling pathways were identified, such as T cell receptor signaling pathway, NF-kappa B signaling pathway and JAK-STAT signaling pathway. The 5-gene diagnostic model could be used to diagnose and guide clinical immunotherapy for sepsis.
Identifiants
pubmed: 37662976
doi: 10.2147/IDR.S418176
pii: 418176
pmc: PMC10473429
doi:
Types de publication
Journal Article
Langues
eng
Pagination
5665-5680Informations de copyright
© 2023 Chen et al.
Déclaration de conflit d'intérêts
All authors declare that they have no conflicts of interest for this work.
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