Transcriptomic analysis of breast cancer patients sensitive and resistant to chemotherapy: Looking for overall survival and drug resistance biomarkers

Purpose: Neoadjuvant chemotherapy is one important therapeutic strategy for breast cancer with the drawback of resistance development. Chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy trying to discover differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Methods: Breast cancer patients who received neoadjuvant chemotherapy were enrolled in this study and according to their pathological response were assigned as sensitive or resistant. To evaluate DEGs, GO, KEGG and protein-protein interactions, RNAseq information from all patients was obtained by next generation sequencing. Results: A total of 1985 DEGs were found and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine-cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs were used further for an analysis of overall survival using the METABRIC study. Seven of those DEGs were found to correlated with overall survival, of them the sub-expression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN and the over expression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival. Conclusions: This work highlights differences at the level of gene expression in patients resistant and sensitive to neoadjuvant chemotherapy. Cellular components related to extracellular region and plasma membrane were mainly involved. Furthermore, 73 DEGs were able to discriminate patients resistant and sensitive to neoadjuvant chemotherapy, and 7 of them were able to predict overall survival. A total of 22 mRNA profile of breast cancer patients prior treatment who were then treated with neoadjuvant chemotherapy