The Landscape of RAD51D in Chinese Ovarian Cancer Patients: Prevalence, Correlation with HRD Score, and Correlation with Efficacy

ABSTRACT

Human genome is continuously threatened by endogenous and exogeneous sources of DNA damage, DNA damage repair (DDR) mechanisms are vital for genome instability and cancer prevention. Homologous recombination repair (HRR) is one of the most important DDR mechanisms because of its high-fidelity. BRCA1/2 have long been the best characterized HRR genes, but other non-BRCA1/2 HRR genes should not be overlooked. In this study, we illustrate that RAD51D is an important non-BRCA1/2 HRR gene in Chinese ovarian cancer patients, from perspectives including prevalence (2.9% patients mutated in RAD51D, 72.7% of RAD51D mutations were bi-allelic loss-of-function [BILOF]), correlation with HRD score (P=0.295 for RAD51D mutation, P=0.087 for RAD51D BILOF), and correlation with efficacy (progression-free survival: HR=0.685 P=0.069 for RAD51D mutation, HR=0.571 P=0.054 for RAD51D BILOF).

Competing Interest Statement

T.S., X.X., Y.L., Z.L., and Y.D. are full-time employees of Precision Scientific (Beijing) Co., Ltd. The remaining authors declare no competing interests.

Funding Statement

This study is a pos-hoc analysis of the first-line adjuvant chemotherapy cohort of EOC-HRD study (Li et al., 2023). EOC-HRD study was supported by a grant from CAMS Innovation Fund for Medical Sciences (CIFMS-2017-I2M-1-002), and grants from the National High Level Hospital Clinical Research Funding (No. 2022-PUMCH-A-117, 2022-PUMCH-B-083, 2022-PUMCH-C-010, 2022-PUMCH-C-022, and 2022-PUMCH-D-003), and the Le Fund (No. KH-2020-LJJ-004, 034, and 035). This study was supported by grants from: 1. The Key Project of Sichuan Provincial Department of Science and Technology (2019YFS0532) (Ethical Lot Number: 20220129); 2. Horizontal Science and Technology Project of Sichuan University (23H1223); 3. The Project of Chengdu Science and Technology Administration (2021-YF05-01725-SN).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study is a post-hoc analysis of the first-line adjuvant chemotherapy cohort of EOC-HRD study (Li et al., 2023). EOC-HRD study was approved by the Ethics Committee of Peking Union Medical College Hospital, Beijing (project ID: JS-1932).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

Raw sequencing data of EOC-HRD study patients cannot be publicly shared as patients did not consent to share raw sequencing data beyond the research and clinical terms. The datasets generated and analyzed might be available upon reasonable request and data usage agreement.

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