目的 探讨RUNX3、P16、DAPK基因启动子DNA甲基化与非小细胞肺癌（non-small cell lung cancer， NSCLC）PD-1抑制剂疗效的关系。 方法 选择2020年1月至2024年1月医院收治的NSCLC患者73例，均接受PD-1抑制剂治疗，根据治疗效果分为疾病进展组（疾病进展）和疾病控制组（完全缓解、部分缓解、稳定）。比较两组的血液样本RUNX3、P16、DAPK基因启动子DNA甲基化情况、肿瘤标志物、肺部CT征象。分析NSCLC患者经PD-1抑制剂治疗后病情持续进展的影响因素。 结果 73例NSCLC患者中完全缓解4例、部分缓解29例疾病稳定25例、疾病进展15例。疾病控制组PD-L1阳性占比高于疾病进展组（P < 0.05）。疾病控制组的RUNX3、P16、DAPK表达水平高于疾病进展组（P < 0.05）。两组病灶密度、病灶边缘、与胸膜关系、血管征象、磨玻璃密度影、钙化、远端阻塞性炎症等CT征象比较，差异无统计学意义（P > 0.05）。两组血清CEA、NSE、CYFRA21-1、CA125水平比较，差异无统计学意义（P > 0.05）。RUNX3细胞（OR = 0.257，95%CI：0.103 ~ 0.644）、P16（OR = 0.243，95%CI：0.096 ~ 0.608）、DAPK（OR = 0.217，95%CI：0.087 ~ 0.543）、PD-L1阳性（OR = 0.242，95%CI：0.096 ~ 0.607）是NSCLC患者经PD-1抑制剂治疗后病情持续进展的影响因素（P < 0.05）。 结论 RUNX3、P16、DAPK基因启动子DNA甲基化与PD-1抑制剂治疗NSCLC的疗效显著相关，低甲基化状态与患者更佳的治疗反应存在关联。

Objective To investigate the association between the promoter DNA methylation of RUNX3， P16， and DAPK genes and the efficacy of programmed death receptor-1 （PD-1） inhibitors in patients with non-small cell lung cancer （NSCLC）. Methods A total of 73 patients with who NSCLC received treatment with PD-1 inhibitors in our hospital from January 2020 to January 2024 were recruited. These patients were then divided into a disease progression group （characterized by progressive disease） and a disease control group （comprising patients with complete response， partial response， and stable disease） based on the therapeutic response. The promoter DNA methylation status of the RUNX3， P16， and DAPK genes in peripheral blood samples， tumor markers， and pulmonary CT features were compared between the two groups. The influencing factors for the sustained disease progression after PD-1 inhibitor therapy were analyzed. Results Among the 73 patients， 4 achieved a complete response， 29 achieved a partial response， 25 had a stable disease state， and 15 experienced disease progression. The proportion of PD-L1-positive cases was significantly higher in the disease control group compared to that in the disease progression group （P < 0.05）. The expression levels of RUNX3， P16， and DAPK were significantly higher in the disease control group than those in the disease progression group （P < 0.05）. No statistically significant differences were detected between the two groups in CT features such as lesion density， lesion margin， pleura relationship， vascular signs， ground-glass opacity， calcification， or distal obstructive inflammation （P > 0.05）. The serum levels of carcinoembryonic antigen （CEA）， neuron-specific enolase （NSE）， cytokeratin 19 fragment （CYFRA21-1）， and cancer antigen 125 （CA125） showed no significant differences between the groups （P > 0.05）. Logistic multivariate regression analysis indicated that RUNX3 （OR = 0.257， 95%CI： 0.103 - 0.644）， P16 （OR = 0.243， 95%CI： 0.096 - 0.608）， DAPK （OR = 0.217， 95%CI： 0.087 - 0.543）， and PD-L1 positivity （OR = 0.242， 95%CI： 0.096 - 0.607） were independent influencing factors for sustained disease progression in NSCLC patients after PD-1 inhibitor therapy （P < 0.05）. Conclusions Promoter DNA methylation of RUNX3， P16， and DAPK is significantly associated with the efficacy of PD-1 inhibitors in the treatment of NSCLC. Moreover， a hypomethylation status is correlated with more favorable therapeutic responses in patients.