ShallowHRD status acts as an effective prognostic predictor in ovarian cancer patients treated by poly (ADP-ribose) polymerase inhibitors (PARPis)

Abstract

Purpose: Homologous recombination deficiency (HRD) plays a crucial role in ovarian cancer patients who are treated with Poly (ADP-ribose) polymerase inhibitors (PARPis). It could be defined as a prognosis biomarker. However, many high throughput sequencing methods for evaluating HRD, including HRDetect (WGS 10X), SigMA (WGS 40X or panel 1000X), and scarHRD (WGS 30X), are technically complex, time and data-storage consuming, and costly. Herein, we aimed to develop a low-cost method by low sequencing coverage to identify HRD status for precision medication.

Methods: We utilized ShallowHRD, a software tool to evaluate tumor HRD based on whole genome sequencing (WGS) at low coverage (1X), and established a novel scoring system, ShallowHRD score system.

Results: Compared with negative ShallowHRD status (ShallowHRD score < 15 or BRCA^wild), positive ShallowHRD status (ShallowHRD score ≥ 15 or BRCA^mut) presented favorable survival after being treated with PARPis.

Conclusion: The ShallowHRD status is a good biomarker for predicting prognosis, which could help guide the clinical application of PARPis in ovarian cancer patients by a cost-effective, time and data-storage saving method.

Keywords: Homologous recombination deficiency; Ovarian cancer; PARPis; ShallowHRD; Whole genome sequencing.