目的：探讨同源重组修复（HRR）基因突变对晚期非小细胞肺癌（NSCLC）患者免疫治疗疗效和预后的影响。方法： 收集2018年3月至2023年4月间在郑州大学第一附属医院接受PD-1抑制剂治疗的124例晚期NSCLC患者的临床资料。根据有 无HRR基因突变将患者分为突变组（n=57例）和野生组（n=67例），采用卡方检验或Fisher’s精确检验比较两组患者的临床特征 及免疫治疗疗效差异，采用Kaplan-Meier方法比较两组患者的PFS，采用单因素和多因素Cox回归分析PFS的影响因素。结果： HRR基因突变组中鳞癌及肿瘤突变负荷（TMB）≥10 mut/Mb 的占比显著多于野生组（54.4% vs 32.8%，61.4% vs 29.9%，均 P<0.05）。HRR基因突变组与野生组患者的ORR分别为17.5%和10.4%（P=0.252），DCR分别为86.0%和73.1%（P=0.080）。HRR 基因突变组与野生组的PFS比较差异具有统计学意义（6.8个月 vs 3.9个月，P<0.001）。多因素分析结果显示，有无HRR基因突变 [HR=0.550，95%C（I 0.352, 0.860）, P=0.009]与免疫治疗线数[HR=0.468，95%C（I 0.312, 0.702）, P<0.001]和PFS显著相关。结论： HRR基因突变组患者的免疫治疗疗效优于野生组患者，HRR基因突变是晚期NSCLC患者免疫治疗预后的独立保护因素。

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 PP=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, PHR=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], PConclusion: 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.

河南省科技攻关项目（No. 222102310052）