Developing a whole exome sequencing-based homologous recombination deficiency test of epithelial ovarian cancer

Abstract

Abstract Background: Homologous recombination deficiency (HRD) test is an important tool to stratify epithelial ovarian cancer (EOC) patients for maintenance therapy. Using whole exome sequencing (WES)-based platform can provide information of gene mutations and HRD score, however, the clinical value of WES-based HRD test was less validated in EOC. Methods: We evaluated the performance of WES-based HRD test by using scarHRD software (https://github.com/sztup/scarHRD) in 44 EOC patients. Samples were concordantly examined using Myriad myChoice® and ACT Genomics. The correlation between HRD status and clinical outcomes was analyzed among the three tests. Results: A high correlation of HRD scores was observed between our WES-based scarHRD test and Myriad (coefficient 0.82, p < 0.001). Compared with positive HRD status in Myriad test, our WES-based scarHRD test had sensitivity, specificity, positive predictive value, and negative predictive value of 93.5%, 76.9%, 90.6%, and 83.3%, respectively. Positive HRD status by our WES-based scarHRD test and Myriad test both were highly associated with advanced FIGO stage and sensitive platinum-response. In multivariate Cox regression analysis, optimal debulking surgery (hazards ratio [HR] 0.39, 95% confidence interval [CI] 0.18–0.84, p = 0.017) and positive HRD status of our test (HR 0.42, 95% CI 0.20–0.90, p = 0.026) were independent factors for the lower risk of disease recurrence. However, the positive HRD status either by Myriad or ACT genomics was not significantly associated with an inferior trend of recurrence. Conclusions Our WES-based scarHRD test provides comprehensive information about gene mutations and HRD scores. It is a new feasible option to determine the HRD status in EOC patients.