LAUSR

Objectives: To investigate the molecular characteristics of high-grade serous ovarian cancer (HGSOC) through integrative analysis of whole exome sequencing (WES) and RNA sequencing (RNA-seq) data. Methods: We used blood samples and primary ovarian cancer tissues that were initially collected from HGSOC patients. Ten patients had germline mutations in either BRCA1 or BRCA2 gene, while 10 patients had wild-type BRCA1/2 genes. We performed WES and RNA-seq on fresh frozen, chemotherapy naive cancer tissues, and matched blood samples. Genomic and transcriptomic profiles were comprehensively compared between patients with germline BRCA1/2 mutation and those with wild type BRCA1/2. Results: 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 index (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 ( Conclusions: We identified the EMT index as a potential prognostic biomarker for HGSOC. Genes related to this index can be therapeutic targets for the treatment of HGSOC.