Identification of the potential crucial hubgenes involved in key pathways predicting pathogenesisand prognosis for breast cancer using integrative analysisof TCGA data

Introduction: Breast cancer (BC) is the second cancer frequentlyoccurring worldwide.This study aimed to identify significantgenes associated with BC through integrative analysisof TCGA data for early detection, prognosis, and treatment ofBC.Materials and Methods: The gene expression profiles ofBRCA were downloaded from The Cancer Genome Atlas (TCGA-BRCA). Data on BRCA and corresponding clinical informationwere downloaded by R package TCGAbiolinks. The R package limma was used to analyze the differentially expressedgenes (DEGs) in BRCA compared to normal tissues. Proteinproteininteraction (PPI) network analysis was employed topredict and explore ۱۰ hub genes using the CytoHubba plug-inof Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopediaof Genes and Genomes (KEGG) enrichment analysesand interrelations of terms and functional groups in biologicalnetwork were performed using clueGo and DAVID database.Survival analyses of the hub genes were carried out using theonline tool Kaplan Meier.Results: In total, ۶۳۱ up-regulated and ۴۳۴ down-regulatedDEGs were identified(P < ۰.۰۵; logFC> ۲). ۱۰ hub genes wereidentified through PPI network analysis, including AURKA,KIF۱۱, DLGAP۵, NCAPG, CCNB۱, CDC۴۵, BIRC۵, BUB۱B,TTK and CDC۲۰. Enrichment of DEGs analysis revealed thatmost of genes are involved in: cell adhesion, mitotic cell cycle,extracellular matrix, P۵۳ signaling, pathways in cancer and oocytemeiosis which may prove their value in clinical applicationsdesigned to treat BC. Survival analysis of hub genes in BCpatients showed a significant correlation between the genes andpatient survival (P < ۰.۰۵).Conclusion: The development of ۱۰ hub genes that were identifiedin this study were validated using previous studies. Survivalanalysis using the Kaplan Meier web tool of prognostic valueproved the hub genes introduced in this research.The findingsof this study deepen our understanding of the molecular mechanismsassociated with BC and suggested that the identified hubgenes may play important roles in BC progression and serve aspotential biomarkers for future prognosis, diagnosis and treatment.