High grade serous ovarian cancer (HGSOC) is conventionally treated with surgery and platinum chemotherapy. The initial response rate is 60-80%, but eventually the majority of patients develop resistance to platinum with subsequent recurrence. Currently, some biomarkers of immune changes, epigenetics, genomic and DNA repair, which are associated with platinum-resistant HGSOC, have been reported, but there is no relatively accurate algorithm to predict whether patients will be resistant to platinum-based therapy.
We performed whole exome sequencing of a total of 111 tissue samples from 40 HGSOC patients as training cohort and 71 HGSOC patients as validation cohort. In the training cohort, the DNA Repair Deficiency score (DRDscore) algorithm was established using LASSO regression with Homologous Recombination Deficiency (HRD) Score, Tumor mutational burden (TMB) and Microhomology insertion deletion (MHID) as the basic parameters, and the accuracy of the DRD model was tested in the validation cohort. According to the consensus statement of Gynecologic Cancer Intergroup (GCOG), we classified Platinum response:(1) Platinum-resistant: progression-free interval since last line of platinum of less than 6 months; (2) Platinum sensitive: progression-free interval since last line of platinum of more than 6 months.Analysis of the accuracy of BRCA1/2 mutation, HRD score and DRD score in estimating platinum-sensitivity chemotherapy.
The platinum-sensitivity rate was 68.57% (24/35) in patients with positive BRCA1/2 mutations, and the platinum-resistance rate was 36.11% (13/36) in patients with negative BRCA1/2 mutations. The platinum-sensitivity rate was 77.5% (31/40) in patients with positive HRDscore, and the platinum-resistance rate was 58.06% (18/31) in patients with negative HRDscore. The platinum-sensitivity rate was 86.53% (45/52) in patients with positive DRDscore, and the platinum-resistance rate was 84.21% (16/19) in patients with negative DRDscore.
DRDscore is a robust prognostic indicator of the risk of platinum-resistance in advanced HGSOC patients. This assessment algorithm for platinum-sensitivity can be used to predict whether HGSOC patients are suitable for platinum-based therapy.
Clinical trial identification
Legal entity responsible for the study
Third Hospital Peking University.
Has not received any funding.
All authors have declared no conflicts of interest.