Clinicopathological and functional evaluation of replication protein A in epithelial ovarian cancers: A target validation study

• Replication Protein A (RPA), a single-stranded DNA (ssDNA)-binding protein is critically involved in DNA replication, checkpoint regulation and DNA repair. • Comprehensive protein and transcriptomic evaluation show that RPA overexpression is linked with aggressive ovarian cancer and platinum resistance. • RPA depletion promoted platinum and PARP inhibitor sensitivity. Replication Protein A (RPA), a single-stranded DNA (ssDNA)-binding protein is critically involved in DNA replication, checkpoint regulation and DNA repair. We evaluated RPA1, 2, and 3 sub-units protein expression in 331 ovarian tumours, transcripts in 1287 tumours and bioinformatics in the ovarian TCGA cohort (n = 379). Platinum resistant ovarian cancer cells were depleted for RPA 1 or 2 and tested for cisplatin, olaparib and talazoparib sensitivity. HAMNO (RPA1 protein-protein interaction inhibitor) was tested in sensitive and resistant cells. High nuclear RPA1 and RPA2 protein was significantly associated with high grade serous ovarian cancers (HGSOC), advanced stage, platinum resistance and worse progression free survival (PFS) (all ps