目的 探讨纳武利尤单抗治疗肺癌的疗效及对患者预后的影响，并探讨疗效与IFN-γ基因突变的相关性。方法 选取邢台医学高等专科学校第二附属医院2020年1月—2021年6月收治的肺癌患者共150例作为研究对象，根据治疗方案不同，将150例患者分为对照组和试验组，每组各75例；纳入同期邢台医学高等专科学校第二附属医院行健康体检的人群100例，设为健康对照组。对照组采用多西他赛进行化疗，试验组应用纳武利尤单抗进行治疗。比较治疗6周后两组疗效，观察用药治疗期间不良反应发生情况，随访记录患者生存情况，分析肺癌患者与健康对照人群IFN-γ基因+874A/T单核苷酸多态性，并分析IFN-γ+874A/T基因多态性与纳武利尤单抗疗效的关系。结果 试验组治疗总有效率为28.0%，高于对照组的14.6%，两组比较差异显著（P＜0.05）；试验组不良反应中脱发、贫血、肌肉酸痛、中性粒细胞减少情况均显著少于对照组（P＜0.05）；试验组疲倦、胃肠道反应发生情况与对照组比较差异无统计学意义（P＜0.05）；随访15个月后，试验组患者中位生存时间为2.500个月（95%CI：2.120～10.425）；对照组患者中位生存时间为4.264个月（95%CI：2.021～11.230）。Log-rank检验显示，两组患者生存情况无显著差异（χ²＝3.84，P=0.912）；肺癌患者IFN-γ+874TT基因型频率和T等位基因频率分别为25.33%、48.6%，显著高于健康对照人群的6.0%、22.0%（P＜0.05）；试验组75例患者中15例有效（20.0%），有效患者中TT基因型与T等位基因占比与无效患者基因型比较，差异显著（P＜0.05）。结论 纳武利尤单抗能够提升肺癌治疗效果，并且具有较高的安全性；IFN-γ+874A/T基因多态性与纳武利尤单抗治疗肺癌疗效可能有关。

Objective To investigate the efficacy of nivolumab in the treatment of lung cancer and its influence on the prognosis of patients, and to explore the relationship between efficacy and IFN-γ gene mutations.Methods A total of 150 patients with lung cancer admitted to the Second Affiliated Hospital of Xingtai Medical College from January 2020 to June 2021 were selected as the study subjects. According to different treatment schemes, 150 patients were divided into control group and test group, with 75 patients in each group. A total of 100 people who were included in the Second Affiliated Hospital of Xingtai Medical College for physical examination in the same period were set as healthy control group. Patients in the control group were treated with docetaxel, and patients in the experimental group were treated with nivolumab. The efficacy of the two groups after six weeks of treatment was compared, and the adverse reactions during drug treatment were observed. The survival time of patients were record in following up period, and the IFN-γ gene +874 A/T single nucleotide polymorphism of lung cancer patients and healthy control population were analyzed and the relationship between IFN-γ+874A/T gene polymorphism and the efficacy of nivolumab was analysed.Results The total effective rate of the test group was 28.0%, higher than that of the control group (14.6%), with a significant difference between the two groups (P <0.05). In the adverse reactions, alopecia, anemia, muscle soreness and neutropenia in the experimental group were significantly less than those in the control group (P <0.05). There was no significant difference in fatigue and gastrointestinal reaction between the experimental group and the control group (P > 0.05). After 15 months of follow-up, the median survival time of patients in the experimental group was 2.500 months (95% CI: 2.120-10.425), and the median survival time of patients in the control group was 4.264 months (95% CI: 2.021-11.230). Log-rank test showed no significant difference in survival between the two groups (χ² = 3.84, P = 0.912). The genotype frequency and T allele frequency of IFN-γ+ 874 TT of lung cancer patients were 25.33% and 48.6%, respectively, which were significantly higher than those of healthy controls (6.0% and 22.0%, P <0.05). Fifteen of the 75 patients in the experimental group were effective (20.0%). The proportion of TT genotype and T allele in effective patients was significantly different from that in ineffective patients (P <0.05).Conclusion Nivolumab can improve the therapeutic effect of lung cancer, and has high safety. IFN-γ+874A/T gene polymorphism may be related to the efficacy of nivolumab in the treatment of lung cancer.

R979.1

邢台市科技局重点研发计划项目(2021ZC178)