同源重组修复基因突变对晚期非小细胞肺癌患者免疫治疗疗效和预后的影响OA北大核心CSTPCD

Objective:To explore the effects of homologous recombination repair(HRR)gene mutations on the immunotherapy efficacy and the prognosis of advanced non-small cell lung cancer(NSCLC)patients.Methods:Clinical data of 124 patients with advanced NSCLC who received PD-1 inhibitor treatment between March 2018 and April 2023 at the First Affiliated Hospital of Zhengzhou University were collected.The patients were divided into the mutant group(n=57 cases)and the wild group(n=67 cases)according to the presence or absence of HRR gene mutations.The differences in clinical characteristics and immunotherapy efficacy between the two groups were analyzed by Chi-square test or Fisher's exact test.Kaplan-Meier method was used to compare the progression-free survival(PFS)of the two groups,and univariate and multivariate Cox regression were employed to analyze the factors affecting PFS.Results:The proportions of squamous cell carcinoma and tumor mutation burden(TMB)≥10 mut/Mb were significantly higher in the HRR gene mutant group than in the wild group(54.4%vs 32.8%,61.4%vs 29.9%,all P<0.05).The objective response rate(ORR)was 17.5%and 10.4%(P=0.252),and the disease control rate(DCR)was 86.0%and 73.1%(P=0.080)for patients in the HRR gene mutant group and the wild group,respectively.There was a significant difference in PFS of the HRR gene mutant group and the wild group(6.8 months vs 3.9 months,P<0.001).Multivariate analysis showed that HRR gene mutations(HR=0.550,95%CI[0.352,0.860],P=0.009)and the number of immunotherapy lines(HR=0.468,95%CI[0.312,0.702],P<0.001)were significantly correlated with PFS.Conclusion:The immunotherapy efficacy of the HRR gene mutant group is better than that of the wild group.HRR gene mutations are an independent protective factor for immunotherapy prognosis of patients with advanced NSCLC.