Biomarker Assessment of Homologous Recombination Deficiency in Epithelial Ovarian Cancer: Association With Progression-Free Survival After Surgery
FRONTIERS IN MOLECULAR BIOSCIENCES(2022)
Abstract
Identifying BRCA mutations and homologous recombination deficiency (HRD) is the key to choosing patients for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy. At present, a large amount of research focuses on the application of HRD detection in ovarian cancer. However, few studies have discussed the relationship between HRD detection and postoperative survival in patients with epithelial ovarian cancer (EOC). This study included 38 consecutive patients with EOC who underwent cytoreduction surgery. Owing to tissue availability, only 29 patients underwent molecular profiling and survival analysis. Overall, 21 (72.4%) tumors had HRD scores of >= 42. Mutations in BRCA were observed in 5/29 (17.2%) patients. In this cohort, an HRD score of >= 42 was more common in serous ovarian tumors. We found no statistically significant association between homologous recombination repair (HRR) genes and HRD scores except for tumor protein P53 (TP53) mutation. We also found a strong positive association between HRD scores and chromosomal instability (CIN). In the survival analysis, an HRD score of >23 was correlated with better postoperative progression-free survival (pPFS). With increased depth of research, an appropriate HRD score threshold may serve as a prognostic tool and should be assessed in future studies to predict the clinical value of PARPi.
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Key words
epithelial ovarian cancer, homologous recombination deficiency, homologous recombination deficiency score, chromosomal instability, postoperative progression-free survival
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