Identification of key molecular pathways and genes in BRCA1 and BRCA2-mutant ovarian cancer: evidence from bioinformatics analysis

Abstract

BRCA1 and BRCA2 mutations significantly increase the risk of breast and ovarian cancers (OC) by affecting crucial cellular processes such as cell cycle regulation, DNA repair, and apoptosis. Despite understanding their broad impacts, the detailed effects on gene expression and signaling pathways in OC remain unclear. This study aims to elucidate these dynamics by analyzing RNA-Seq data from 24 OC patients with BRCA1/2 mutations and controls using advanced molecular techniques. Differential expression analysis identified 6136 DEGs in BRCA1-mutant and 3615 DEGs in BRCA2-mutant OCs, with 2041 overlapping DEGs. These shared genes underwent Gene Ontology (GO), KEGG, and Protein–protein interaction (PPI) network analyses, revealing pathways like MyD88-independent TLR signaling and mRNA vaccine activation of dendritic cells. Key genes (TRAF3, TICAM1, IRF7, CD40, IRF3, SARM1, RAB11FIP, and PRKCE) involved in TRIF-dependent TLR signaling showed distinct expression patterns in BRCA1/2-deficient OCs. The top 10 hub genes identified were evaluated for their prognostic significance using the Kaplan–Meier Plotter database. The findings highlight the genetic landscape and pathways altered by BRCA1/2 mutations in OC, offering insights for improved diagnostics and personalized treatments. Additionally, the impact on immunosurveillance through the TRIF-dependent TLR system suggests new immunotherapeutic strategies for OC patients with BRCA1/2 mutations, addressing the challenge of cancer recurrence.

Keywords

BRCA1 / BRCA2 / Ovarian cancer / Breast cancer / Bioinformatics analysis

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