Abstract
<h3>Objectives:</h3> 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. <h3>Methods:</h3> We used blood samples and primary ovarian cancer tissues that were initially collected from HGSOC patients. Ten patients had germline mutations in either <i>BRCA1</i> or <i>BRCA2</i> gene, while 10 patients had wild-type <i>BRCA1/2</i> genes. We performed WES and RNA-seq on fresh frozen, chemotherapy naïve cancer tissues, and matched blood samples. Genomic and transcriptomic profiles were comprehensively compared between patients with germline <i>BRCA1/2</i> mutation and those with wild type <i>BRCA1/2.</i> <h3>Results:</h3> HGSOC samples initially divided into two groups by the presence of germline <i>BRCA1/2</i> 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 (<i>P</i>=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) (<i>P</i>=0.030). <h3>Conclusions:</h3> 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.
Highlights
Ovarian cancer, one of the deadliest gynecologic malignancies, is a global burden with an estimated 313,959 new cases and 207,252 cancer deaths each year [1]
Between the gBRCA1/2mut and gBRCA1/2wt groups, no differences were observed in baseline clinicopathologic characteristics (Table 1)
We investigated the molecular characteristics of High-grade serous ovarian cancer (HGSOC) through an integrative analysis of genomic and transcriptomic data obtained from chemotherapy-naïve primary HGSOC tissues
Summary
One of the deadliest gynecologic malignancies, is a global burden with an estimated 313,959 new cases and 207,252 cancer deaths each year [1]. The patients’ BRAC1/2 mutational status is of high interest because several poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors are currently available for the treatment of primary and recurrent HGSOC, based on the phase 3 clinical trials, which have demonstrated the significant survival benefit brought by PARP inhibitors [4,5,6,7,8]. In breast cancer, loss of BRCA1 protein is associated with EMT [12]. Such a relationship has been poorly investigated in ovarian cancer. Broadening the molecular understanding of HGSOC and elucidating the underlying mechanisms for EMT in terms of BRCA1/2 gene alterations is expected to open a new horizon in the treatment of HGSOC [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
