RNA Sequencing Analysis for the Identification of Genes Associated with Cisplatin Resistance in Ovarian Cancer

Abstract Cisplatin is a drug of choice for the treatment of ovarian cancer (OC). However, the development of resistance to platinum-based drugs is common, causing relapse and complicating the clinical management of these patients. The identification of biomarkers of resistance can contribute to a better stratification of the patients for treatment strategies. This study compared the transcriptional profile of two cisplatin-resistant OC cell lines, OV90CisR1 and OV90CisR2, to their sensitive counterpart, OV90. R-tool was used for the screening of significant differentially expressed genes (DEGs, p ≤ 0.05), gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) analyses. In the top-ranked GO terms, we found extracellular matrix (ECM) and actin filament-related pathways. Consequently, we observed a high expression of integrins (ITGA1, ITGA6, ITGA11, and ITGAV), collagen (COL3A1, COL4A1, COL7A1, COL11A1), fibronectin (FN1) and other related proteins in the PPI analysis. The analysis shows how these factors show alteration in ECM composition and reorganization of the actin cytoskeleton, further supported by the overexpression of metallopreoteases (ADAMTS2, ADAMTS7, ADAMTSL1, and ADAMTSL4) as evident in the PPI network. We conclude that these changes in ECM could stimulate integrins and facilitate epithelial to mesenchymal transition (EMT) through pathways like Wnt signaling. Transition to a mesenchymal phenotype can cause drastic changes in the membrane transport e.g., highly expressed ABC efflux transporters (ABCA5, ABCD2) in the present case, which can lead to drug resistance.