Classification of high-grade serous ovarian carcinoma by epithelial-to-mesenchymal transition signature and homologous recombination repair genes

High-grade serous ovarian cancer (HGSOC) is one of the deadliest cancers that can occur in women. This study aimed to investigate the molecular characteristics of HGSOC through integrative analysis of whole exome sequencing (WES) and RNA sequencing (RNA-seq) data. We used fresh-frozen, chemotherapy-naïve primary ovarian cancer tissues and matched blood samples of HGSOC patients and conducted next generation WES and RNA-seq. Genomic and transcriptomic profiles were comprehensively compared between ten patients with germline BRCA1/2 mutation and the other ten patients with wild type BRCA1/2. HGSOC samples initially divided into two groups by the presence of germline BRCA1/2 mutations showed mutually exclusive mutational patterns. Implementation of RNA-seq and application of epithelial-to-mesenchymal transition (EMT) index onto the HGSOC samples revealed that they can be divided into two subtypes; homologous recombination repair (HRR)-activated and mesenchymal. Patients with mesenchymal HGSOC, characterized by the activation of EMT transcriptional program, low genomic alteration and diverse cell-type compositions, exhibited significantly worse overall survival than did those with HRR-activated HGSOC (P=0.002). By applying the EMT index to TCGA HGSOC data, patients with high EMT index (≥ the median) showed significantly worse overall survival than did those with low EMT index (< the median) (P=0.030). In conclusion, we identified EMT index as a potential prognostic biomarker for HGSOC. Genes related to this index can be therapeutic targets for the treatment of HGSOC.