Identification of key genes in non-functioning pituitary adenoma using gene expression profile and protein-protein interaction network

The non-functioning pituitary adenoma (NFPA) is a common intracranial tumor with local invasive potential and a high recurrence rate . The only treatment options are surgery and radiation . There is an urgent need to develop novel therapeutic strategies to reduce the recurrence rate of NFPAs, either through biomarkers or medical therapies. We aimed to identify biomarkers and biological pathways associated with the progression of NFPA by construction and analysis of protein-protein interaction (PPI) network based on differentially expressed genes (DEGs). Methods:A microarray dataset (GSE۲۶۹۶۶) from Gene Expression Omnibus (GEO) was employed to determine DEGs between normal pituitary tissues and NFPA tissues. DEGs were identified using GEOquery and Limma packages. DEGs were mapped on experimentally confirmed PPIs retrieved from the IntAct database (۰۲-۲۰۲۲). The constructed PPI network’s topological analyses (Degree, Betweenness, and Closeness centrality) were performed using the igraph package. Functional clusters were identified using the MCL package. The enrichment of clusters was performed using the Enrichr database.Results:We identified ۱۱۳۵ DEGs in the NFPA dataset considering adjusted p-values <۰.۰۵ and log fold change>۲. The constructed PPI network was analyzed, and high-centrality genes were identified. Using functional analysis of clusters, we identified potential candidate genes in NFPA, which were the more central genes in the PPI network and involved in biological pathways. EGFR, MET, KIT, ERBB۴, and BNDF, enriched in the MAPK signaling pathway and Ras signaling pathway, CDKN۱A, and CDKN۲A, enriched in the cell cycle, FGFR۳, enriched in the regulation of actin cytoskeleton, STAT۳, enriched in JAK-STAT signaling pathway, and HSPA۲, enriched in protein processing in the endoplasmic reticulum, were identified as key candidate genes. Conclusion:This study provides new insights into network biomarkers that may be potential therapeutic targets in NFPA

کلیدواژه ها:

Non-functioning pituitary adenoma (NFPA) ، gene expression ، protein-protein interaction network (PPI) ، systems biology