The clinical pathological characteristics and prognostic Relevance of Homologous Recombination Repair Gene Mutations in Ovarian Cancer Patients：A Retrospective Cohort Study

Backgrouds ：Whether homologous recombination repair (HRR) mutation has a differential effect on prognosis has not been confirmed by current studies. The purpose of this retrospective study was to explore the clinical importance, prognostic value, and frequency of pathogenic changes in HRR genes in patients with ovarian cancer. Methods: We analyze information including gene mutation and clinical prognosis of patients with both ovarian cancer and HRR mutation in the TCGA-OV database. We sequenced DNA from blood and/or neoplasm from 98 women, all patients included in this retrospective study were admitted to Shanghai General Hospital between January 2021and May 2024, and HRR mutation including germline BRCA1/2 mutation were tested，Defects in HRR were defined as damaging mutations in genes. All patients with NAC received platinum-containing chemotherapy. All relevant medical records were collected. Including Seventy-four of these patients had a follow-up time. Results: By layering the data based on the median Tumor Mutation Burden (TMB) value in the TCGA-OV database, we uncovered a significant disparity in OS between the TMB-Low and TMB-High groups(p<0.05). The predicted odds of death and OS <763 days in nomograms incorporating the expression of HRR genes in the TCGA-OV database as an influencing factor were 0.209 and 0.0876, respectively,indicated that up regulation of RAD51 family members and down regulation of PALB2, ATM and BRCA2 might predicate well prognosis. A total of 98 patients were enrolled, including 70 with HRR mutations (HRRmt) and 28 with HRR wild-type (HRRwt).And We collected survival forecast data from 74 patients,including 50 with HRR mutations (HRRmt) and 24 with HRR wild-type (HRRwt).Ten patients underwent secondary debulking surgery combined with chemotherapy upon recurrence. We identified significant differences in the size of the initial debulking surgery achieving R0 status (p=0.005), the low CA125 levels(<1000 U/ml) at diagnosis (p=0.015) and the use of PARPi (p=0.024) and Anti-angiogenic drugs(p＜0.001), these are major factors influencing the progression-free survival (PFS) of ovarian cancer patients. For HRRmt patients PARPi use significantly impacted PFS (p=0.049). Kaplan-Meier analysis showed that patients achieving R0 had longer mean PFS (41.37 months vs. 31.40 months, p=0.002) across both groups. HRR mutations, including non-BRCA genes, did not significantly prolong PFS or disease-free survival (DFS) in ovarian cancer, highlighting the need for stratification in clinical trials. PARPi use (p=0.049) and achieving R0 status (p=0.005) significantly affected PFS in HRRmt patients, who also showed higher sensitivity to PARPi, with a statistically significant difference in prognosis between users and non-users. Conclusions： This study suggests that HRR gene mutations hold potential as a prognostic indicator in ovarian cancer, aiding in refined HRD assessment and identifying patients likely to respond to PARPi therapy. Prospective studies continuously observing mutation patterns can enhance understanding of HRR mutation developments and resistance mechanisms, guiding future treatment strategies.