Up-regulation of FN1, Activation of Maturation Promoting Factor and Associated Signaling Pathway Facilitates Epithelial-Mesenchymal Transition, Inhibits Apoptosis and Elevates Proliferation Rate of Breast Cancer Cells: In Silico Analysis of Microarray Datasets

Background: Knowing that the molecular mechanisms underlying breast cancer (BC) are not yet fully understood it was considered worth to launch investigation for the detection of key molecular pathways and associated genes and proteins. Methods: : In total two microarray based datasets (GSE10810 and GSE29431), consisting of 89 breast cancer samples and 31 controls, were retrieved from the Gene Expression Omnibus (GEO) database and processed to identify the differentially expressed genes (DEGs). The pathway and functional enrichment analyses of DEGs were performed using DAVID online tool. Protein-Protein interaction (PPI) network was constructed using an online tool STRING and visualized through Cytoscape software to identify the significant module and hub genes via MCODE and Cytohubba applications. The identified hub genes were then further analyzed to document their response in Kaplan-Meier (KM) survival curve analysis, investigate differential expression profile and its correlation with promoter’s methylation status, and finally for the construction of the gene-drug interaction network. Results: : In total 449 DEGs were detected including 151 up-regulated and 298 down-regulated genes. The identified DEGs were enriched in various cancer related biological functions and pathways. Based on PPI network analysis of the DEGs, six hub genes, CDK1, FN1, AURKA, CCNB2, BIRC5, and TOP2A, were correlated with worse overall survival (OS) of the breast cancer patients. Conclusion: The extensive in silico analysis has been helpful to evaluate evidence highlighting the prominent role played by the identified hub genes in stimulating breast tumor growth through the activation of Maturation Promoting Factor (MPF), PI3K/AKT signaling, and associated pathways that could be targeted for devising effective treatment strategies.