Dataset Information

Biomarker Assessment of Homologous Recombination Deficiency in Epithelial Ovarian Cancer: Association With Progression-Free Survival After Surgery.

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.

SUBMITTER: Yi H

PROVIDER: S-EPMC9234295 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Biomarker Assessment of Homologous Recombination Deficiency in Epithelial Ovarian Cancer: Association With Progression-Free Survival After Surgery.

Yi Huan H Li Linhong L Huang Jimiao J Ma Zhiming Z Li Hongping H Chen Jian J Zheng Xiangqin X Chen Jingjing J He Haixin H Song Jianrong J

Frontiers in molecular biosciences 20220613

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 ...[more]

PMID: 35769916

Similar Datasets

Project description:BackgroundThe homologous recombination deficiency (HRD) test is an important tool for identifying patients with epithelial ovarian cancer (EOC) benefit from the treatment with poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi). 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.MethodsWe enrolled 40 patients with EOC in the training cohort and 23 in the validation cohort. The WES-based HRD score was calculated using the scarHRD software. We first evaluated the concordance of the HRD status defined by the Myriad MyChoice CDx and then assessed the value of HRD on clinical prognosis in patients with EOC.ResultsThe HRD score defined by the WES-based test was positively correlated with that of the Myriad MyChoice® CDx test (r = 0.82, p < 0.01) in the training cohort. In compared to HRD status of Myriad test, the sensitivity, specificity, positive predictive value, and negative predictive value of the WES-based HRD test were 93.5% (29/31), 77.8% (7/9), 93.5% (29/31), and 77.8% (7/9), respectively. Patients with positive HRD status defined by WES-based scarHRD test and Myriad MyChoice® CDx test were both highly associated with platinum sensitive response (both Fisher's exact test, p = 0.002) as well as the superior progression-free survival (both log-rank p = 0.002). The multi-variate Cox regression model incorporated with optimal debulking surgery showed that the recurrence risk was decreased in the patients with positive HRD status, either defined by Myriad MyChoice® CDx test (Hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.14-0.79, p = 0.013) or WES-based test Myriad MyChoice® CDx test (HR 0.34, 95% CI 0.14-0.80, p = 0.014). Nine patients had mutations in the genes involved in HR DNA repair, and all of them were positive for HRD. In the validation group, 23 patients were defined as positive HRD by WES-based testing. Six positive HRD patients and 5 negative HRD patients received maintenance PARPi. The median responsive interval of PARPi was 17 months in positive HRD patients and 3 months in negative HRD patients.ConclusionThe WES-based test is a potential option for determining the HRD status in EOC patients, and desires for further validation in large-scale cohorts.

Dataset Information

Biomarker Assessment of Homologous Recombination Deficiency in Epithelial Ovarian Cancer: Association With Progression-Free Survival After Surgery.

Publications

Biomarker Assessment of Homologous Recombination Deficiency in Epithelial Ovarian Cancer: Association With Progression-Free Survival After Surgery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets