探讨动态监测循环肿瘤DNA(circulating tumor DNA, cfDNA)、中性粒细胞与淋巴细胞比值(neutrophil lymphocyte ratio, NLR)及程序性死亡配体-1信使核糖核酸(programmed cell death ligand 1 mRNA, PD-L1 mRNA)对非小细胞肺癌(non-small cell lung cancer, NSCLC)患者免疫治疗疗效及预后的预测意义。

选取2019年1月至2022年6月我院收治的42例晚期NSCLC患者，根据免疫治疗疗效分为观察组22例和对照组20例。治疗前后检测cfDNA浓度、NLR及PD-L1 mRNA表达水平，计算指标变化率。采用受试者工作特征曲线(receiver operating characteristic, ROC)分析单一指标及联合模型对客观缓解率(objective response rate, ORR)的预测，采用Cox比例风险回归分析指标动态变化与无进展生存期(progression-free survival, PFS)的关联。

观察组治疗后cfDNA、NLR、PD-L1 mRNA低于对照组，变化率绝对值大于对照组(P<0.05)。观察组较对照组cfDNA变化率[(－24.46±8.11)%比(－16.40±8.93)%，t＝3.064，P＝0.004]; NLR变化率[(－24.51±6.86)%比(－15.75±10.65)%，t＝3.196，P＝0.003]; PD-L1 mRNA变化率[(－20.29±5.89)%比(－15.83±5.10)%，t＝2.607，P＝0.013]。ROC曲线分析显示，cfDNA变化率、NLR变化率、PD-L1 mRNA变化率预测ORR的曲线下面积(area under the curve, AUC)分别为0.761(95%CI：0.605~0.879)、0.748(95%CI：0.590~0.869)、0.732(95%CI：0.573~0.857)，三者联合预测AUC为0.895(95%CI：0.762~0.968)，灵敏度为90.91%，特异度为80.00%，优于单一指标。多因素Cox回归分析显示，cfDNA变化率≤20%(HR＝6.541，95%CI：1.336~31.333，P＝0.019)、NLR变化率≤22%(HR＝7.910，95%CI：1.538~40.684，P＝0.013)及PD-L1 mRNA变化率≤20%(HR＝6.501，95%CI：1.038~40.705，P＝0.045)是NSCLC患者免疫治疗PFS缩短的危险因素。

动态监测cfDNA、NLR及PD-L1 mRNA可有效预测NSCLC患者免疫治疗疗效及预后，三者联合预测可为临床个体化治疗决策提供参考。

To investigate the predictive value of dynamic monitoring of circulating tumor DNA (cfDNA), neutrophil-to-lymphocyte ratio (NLR), and programmed cell death ligand 1 messenger RNA (PD-L1 mRNA) for immunotherapy efficacy and prognosis in patients with non-small cell lung cancer (NSCLC).

A total of 42 patients with advanced NSCLC admitted to our hospital from January 2019 to June 2022 were selected and divided into an observation group 22 cases and a control group 20 cases based on immunotherapy efficacy. cfDNA concentration, NLR, and PD-L1 mRNA expression levels were measured before and after treatment, and the rate of change for each indicator was calculated. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of single indicators and the combined model for objective response rate (ORR). Cox proportional hazards regression was used to analyze the association between dynamic changes in the indicators and progression-free survival (PFS).

After treatment, cfDNA, NLR, and PD-L1 mRNA levels in the observation group were lower than those in the control group, and the absolute values of the rate of change were greater than those in the control group (P<0.05). Compared with the control group, the observation group showed: cfDNA rate of change [(-24.46±8.11)% vs. (-16.40±8.93)%, t=3.064, P=0.004]; NLR rate of change [(-24.51±6.86)% vs. (-15.75±10.65)%, t=3.196, P=0.003]; PD-L1 mRNA rate of change [(-20.29±5.89)% vs. (-15.83±5.10)%, t=2.607, P=0.013]. ROC curve analysis showed that the area under the curve (AUC) for predicting ORR was 0.761 (95%CI: 0.605~0.879) for cfDNA rate of change, 0.748 (95%CI: 0.590~0.869) for NLR rate of change, and 0.732 (95%CI: 0.573~0.857) for PD-L1 mRNA rate of change. The combined model of the three indicators yielded an AUC of 0.895 (95%CI: 0.762~0.968), with a sensitivity of 90.91% and a specificity of 80.00%, which was superior to any single indicator. Multivariate Cox regression analysis showed that cfDNA rate of change ≤20% (HR=6.541, 95%CI: 1.336~31.333, P=0.019), NLR rate of change ≤22% (HR=7.910, 95%CI: 1.538~40.684, P=0.013), and PD-L1 mRNA rate of change ≤20% (HR=6.501, 95%CI: 1.038~40.705, P=0.045) were risk factors for shortened PFS in NSCLC patients receiving immunotherapy.

Dynamic monitoring of cfDNA, NLR, and PD-L1 mRNA can effectively predict immunotherapy efficacy and prognosis in NSCLC patients. The combination of these three indicators provides a reference for clinical individualized treatment decisions.