Expression Of RAD51 Gene In Platinum-sensitive Recurrent Ovarian Cancer And Its Correlation With Parp Inhibitor(Niraparib)resistance

Objective:As an important gene of HR pathway,RAD51 protein expression plays an important role in the occurrence and development of ovarian cancer and the restoration of homologous recombination pathway.Therefore,the purpose of this study was to investigate the expression of RAD51 protein in platinum-sensitive recurrent high grade serous ovarian cancer and its effect on drug sensitivity to Niraparib,and to investigate the feasibility of RAD51 combined with BRCA detection as a molecular marker to predict the efficacy of PARPi.Methods:Clinical follow-up data of 56 patients in line with this study were retrospectively analyzed.And 8 normal ovarian tissues were selected as the control,and the expression of HR repair key protein RAD51 in paraffin specimens was detected by immunohistochemical staining(IHC).Second-generation high-throughput sequencing(NGS)was used to detect mutations in the BRCA genes of patients eligible for the study.The survival and prognostic status of eligible patients at the end of the study,the time of initiation of Niraparib,and the time from initiation of Niraparib to tumor recurrence were evaluated.progression-free survival(PFS)after Niraparib maintenance was recorded,and the prognostic factors were statistically analyzed.Results:1.Protein immunohistochemical results showed that the positive rate of RAD51 in platinum-sensitive recurrent High grade serous ovarian cancer(HGSOC)was significantly higher than that in normal ovarian epithelial tissue(P < 0.05).2.The second-generation high-throughput sequencing results showed that among all the platinum-sensitive relapsing HGSOC patients who completed sequencing,12 patients had BRCA mutations,accounting for 21.42% of the total number of 56 patients with platinum-sensitive relapsing HGSOC.3.Multivariate risk analysis of PFS after oral Niraparib in patients eligible for this study showed that RAD51 protein expression was another factor to determine the maintenance effect of oral nylapalil toluesulfonic acid in platinum-sensitive relapsing HGSOC patients following BRCA mutation status.Conclusion:1.High expression of RAD51 protein was significantly associated with patients’ susceptibility to oral Niraparib and could be used as a potential molecular marker for predicting PARPi efficacy in patients with platinum-sensitive recurrent HGSOC.2.The expression of RAD51 protein is closely related to the prognosis of advanced platinum-sensitive relapsing HGSOC,and can be used as an indicator to predict the prognosis of platinum-sensitive relapsing HGSOC.3.The expression of RAD51 protein is significantly correlated with the presence or absence of BRCA mutations in patients.The combination of the two can more accurately judge the prognosis of patients.