Identification of hub genes associated with EMT-induced chemoresistance in breast cancer using integrated bioinformatics analysis.

Chemoresistance is one of the major challenges in the treatment of breast cancer. Recent evidence suggests that epithelial-to-mesenchymal transition (EMT) plays a critical role in not only metastasis but also in chemoresistance, hence causing tumor relapse. This study aimed to identify the hub genes associated with EMT and chemoresistance in breast cancer affecting patient/clinical survival. Commonly differentially expressed genes (DEGs) during EMT and chemoresistance in breast cancer cells were identified using publicly available datasets, GSE23655, GSE39359, GSE33146 and GSE76540. Hierarchical clustering analysis was utilized to determine the commonly DEGs expression pattern in chemoresistant (CR) breast cancer cells. GSEA revealed that EMT-related genes sets were enriched in the CR samples. Further, we found that EMT-induced breast cancer cells showed overexpression of drug efflux transporters along with resistance to chemotherapeutic drug. Pathway enrichment analysis revealed that the commonly DEGs were enriched in immunological pathways, early endosome, protein dimerization, and proteoglycans in cancer. Further, we identified eight hub genes from the protein-protein interaction (PPI) network. We validated the gene expression levels of the hub genes among TCGA breast cancer samples using UALCAN. Survival analysis for the hub genes was performed using KM plotter, which showed a worse relapse-free survival (RFS) of the hub genes among breast cancer patients. In conclusion, this study identified eight hub genes that play an important role in the pathways underlying EMT-induced chemoresistance in breast cancer and can be used as therapeutic targets after clinical validation.