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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2026, Vol. 19 ›› Issue (04) : 607 -614. doi: 10.3877/cma.j.issn.1674-6902.2026.04.012

论著

中性粒细胞/淋巴细胞比值预测免疫治疗联合化疗晚期NSCLC患者预后的临床意义
陈玥1, 吴丙琳1, 冯妮娜1, 杨勤秦1, 苗雄伟2, 尚苗苗3, 马静4,†(), 王欢4, 任巧微1,†()   
  1. 1716000　延安，延安市人民医院检验科
    2716000　延安，延安市人民医院肿瘤科
    3716000　延安，延安市人民医院呼吸内科
    4716000　延安，延安市人民医院病理科
  • 收稿日期:2026-03-25 出版日期:2026-08-25
  • 通信作者: 马静, 任巧微
  • 基金资助:
    陕西省青年人才托举计划(2021-1-2)

Clinical significance of neutrophil-to-lymphocyte ratio in predicting prognosis of advanced lung cancer patients receiving immunotherapy combined with chemotherapy

Yue Chen1, Binglin Wu1, Nina Feng1, Qinqin Yang1, Xiongwei Miao2, Miaomiao Shang3, Qiaowei Ren1,†()   

  1. 1Department of Clinical Laboratory, Yan′an People′s Hospital, Yan′an 716000, China
    2Department of Oncology, Yan′an People′s Hospital, Yan′an 716000, China
    3Department of Respiratory Medicine, Yan′an People′s Hospital, Yan′an 716000, China
    4Department of Pathology, Yan′an People′s Hospital, Shaanxi, Yan′an 716000, China
  • Received:2026-03-25 Published:2026-08-25
  • Corresponding author: Qiaowei Ren
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引用本文：

陈玥, 吴丙琳, 冯妮娜, 杨勤秦, 苗雄伟, 尚苗苗, 马静, 王欢, 任巧微. 中性粒细胞/淋巴细胞比值预测免疫治疗联合化疗晚期NSCLC患者预后的临床意义[J/OL]. 中华肺部疾病杂志(电子版), 2026, 19(04): 607-614.

Yue Chen, Binglin Wu, Nina Feng, Qinqin Yang, Xiongwei Miao, Miaomiao Shang, Qiaowei Ren. Clinical significance of neutrophil-to-lymphocyte ratio in predicting prognosis of advanced lung cancer patients receiving immunotherapy combined with chemotherapy[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2026, 19(04): 607-614.

目的

探讨晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者一线免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)联合化疗疗效的预测生物标志物，构建预后评分模型。

方法

选择2022年10月至2025年10月我院收治的接受一线ICIs联合化疗晚期NSCLC患者125例，分析治疗反应。通过LASSO回归筛选变量，基于中性粒细胞-淋巴细胞比值(neutrophiltolymphocyte ratio, NLR)、乳酸脱氢酶(lactate dehydrogenase, LDH)、白蛋白(albumin, ALB)及肝转移构建NLAL评分系统，0~1分低风险组95例，2~5分高风险组30例。依据NLR>3.25为观察组，NLR≤3.25为对照组。采用受试者工作特征(receiver operating characteristic, ROC)曲线、多因素Cox比例风险回归和KaplanMeier曲线分析无进展生存期(progressionfree survival, PFS)。

结果

低风险组疾病控制率(disease control rate, DCR)为84.21%，显著高于高风险组60.00%(χ2＝7.892，P＝0.005)；低风险组客观缓解率(objective response rate, ORR)高于高风险组[40.00%(38/95)比10.00%(3/30)，χ2＝9.310，P＝0.002]。NLAL评分预测DCR的曲线下面积(area under the curve, AUC)为0.797(95%CI：0.665~0.872)，优于单一指标NLR(AUC＝0.735)、LDH(AUC＝0.752)、ALB(AUC＝0.718)、肝转移(AUC＝0.689)及PDL1表达(AUC＝0.578)(P<0.05)。多因素Cox回归显示，肝转移(HR＝1.524，95%CI：1.032~2.248，P＝0.034)、NLR>3.25(HR＝1.854，95%CI：1.247~2.766，P＝0.003)、LDH>225 U/L(HR＝1.654，95%CI：1.114~2.452，P＝0.013)及ALB<36.52 g/L(HR＝1.416，95%CI：1.005~1.996，P＝0.046)为PFS缩短的危险因素。低风险组中位PFS长于高风险组(15.31个月比6.78个月，Logrank P<0.001)。NLAL评分预测PFS的AUC为0.763(95%CI：0.689~0.821)，优于单一指标(P<0.05)。中位随访19个月，72例生存(57.60%)、死亡53例(42.40%)。

结论

基于NLR、LDH、ALB及肝转移构建的NLAL评分可预测一线ICIs联合化疗晚期NSCLC患者的ORR、DCR及PFS，优于单个外周血指标及PDL1表达，具有临床意义。

关键词: 非小细胞肺癌, 免疫检查点抑制剂, 化疗, 中性粒细胞-淋巴细胞比值, 乳酸脱氢酶, 预后
Objective

To explore predictive biomarkers for the efficacy of firstline immune checkpoint inhibitors (ICIs) combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to construct a prognostic scoring model.

Methods

A total of 125 patients with advanced NSCLC who received firstline ICIs plus chemotherapy in our hospital from October 2023 to October 2025 were enrolled, and treatment responses were analyzed. Variables were screened by LASSO regression, and the NLAL scoring system was constructed based on neutrophiltolymphocyte ratio (NLR), lactate dehydrogenase (LDH), albumin (ALB), and liver metastasis. Patients were divided into a lowrisk group (0-1 point, 95 cases) and a highrisk group (2–5 points, 30 cases). Patients were divided into the observation group (NLR>3.25) and the control group (NLR<3.25). Progressionfree survival (PFS) was analyzed using receiver operating characteristic (ROC) curves, multivariate Cox proportional hazards regression, and KaplanMeier curves.

Results

The disease control rate (DCR) in the lowrisk group was 84.21%, significantly higher than that in the highrisk group (60.00%) (χ2=7.892, P=0.005); the objective response rate (ORR) was also higher in the lowrisk group [40.00% (38/95) vs. 10.00% (3/30), χ2=9.310, P=0.002]. The area under the curve (AUC) of the NLAL score for predicting DCR was 0.797 (95%CI: 0.665~0.872), which was superior to single indicators including NLR (AUC=0.735), LDH (AUC=0.752), ALB (AUC=0.718), liver metastasis (AUC=0.689), and PDL1 expression (AUC=0.578) (all P<0.05). Multivariate Cox regression showed that liver metastasis (HR=1.524, 95%CI: 1.032~2.248, P=0.034), NLR>3.25 (HR=1.854, 95%CI: 1.247~2.766, P=0.003), LDH>225 U/L (HR=1.654, 95%CI: 1.114~2.452, P=0.013), and ALB<36.52 g/L(HR=1.416, 95%CI: 1.005~1.996, P=0.046) were risk factors for shorter PFS. The median PFS was longer in the lowrisk group than in the highrisk group (15.31 months vs. 6.78 months, logrank P<0.001). The AUC of the NLAL score for predicting PFS was 0.763 (95%CI: 0.689~0.821), superior to single indicators (P<0.05). With a median followup of 19 months, 72 patients (57.60%) survived and 53 (42.40%) died.

Conclusion

The NLAL score based on NLR, LDH, ALB, and liver metastasis can predict ORR, DCR, and PFS in advanced NSCLC patients receiving firstline ICIs combined with chemotherapy, and it is superior to single peripheral blood biomarkers and PDL1 expression, demonstrating clinical utility.

Key words: Nonsmall cell lung cancer, Immune checkpoint inhibitors, Chemotherapy, Neutrophiltolymphocyte ratio, Lactate dehydrogenase, Prognosis
表1 晚期NSCLC患者临床资料结果[n(%)]
临床资料 观察组(n＝51) 对照组(n＝74) t/χ2值 P值
吸烟史 32(62.75) 52(70.27) 0.776 0.379
临床分期     8.677 0.003
Ⅲ期 5(9.80) 24(32.43)    
Ⅳ期 46(90.20) 50(67.57)    
ICIs类型     0.332 0.565
PD-1抑制剂 44(86.27) 61(82.43)    
PD-L1抑制剂 7(13.73) 13(17.57)    
化疗方案     0.243 0.622
培美曲塞 33(64.71) 51(68.92)    
白蛋白紫杉醇 18(35.29) 23(31.08)    
既往胸部放疗史 5(9.80) 7(9.46) 0.004 0.949
既往根治性手术史 7(13.73) 13(17.57) 0.332 0.565
肝转移 12(23.53) 10(13.51) 2.088 0.148
PD-L1 TPS     0.270 0.603
TPS<1% 32(62.75) 43(58.11)    
TPS≥1% 19(37.25) 31(41.89)    
图1 晚期NSCLC患者组织病理学图。图A为肿瘤细胞边缘呈栅栏状(HE×10)；图B为肿瘤细胞浸润性生长(HE×20)；图C为肿瘤细胞黏附性差，个别细胞呈印戒样(HE×10)；图D为肿瘤细胞呈腺样排列(HE×10)
图2 晚期NSCLC患者ICIs联合化疗前后胸部CT图。图A为治疗前右肺下叶可见不规则软组织密度实变影，周边伴有肺大疱，肿瘤与大疱边界不清；图B为治疗后复查胸部CT示，原发肿瘤病灶实变区域显著缩小，大疱周围的软组织影明显减少，经实体肿瘤反应标准评估达PR;图C为治疗前基线胸部CT示，右肺中下叶可见巨大不规则软组织密度肿块实变影，病变体积大，并伴有大量右侧胸腔积液；图D为治疗后复查胸部CT示，右肺中下叶肿块实变影增大，病变范围弥漫，原胸腔积液依然存在，经实体肿瘤反应标准评估为PD
表2 晚期NSCLC ICIs联合化疗疗效影响因素分析
临床资料及影响因素 PR(n) SD(n) PD(n) 合计[n(%)] ORR(%) χ2值 P值 DCR(%) χ2值 P值
临床特征                      
  病理类型           0.629 0.730   0.011 0.994
  腺癌 20 27 13 60(48.00) 33.33     78.33    
  鳞癌 13 19 9 41(32.80) 31.71     78.05    
  其他 8 11 5 24(19.20) 33.33     79.17    
  临床分期           1.261 0.262   2.825 0.093
  Ⅲ期 12 14 3 29(23.20) 41.38     89.66    
  Ⅳ期 29 43 24 96(76.80) 30.21     75.00    
  既往根治性手术史           0.085 0.771   0.036 0.850
  有 6 10 4 20(16.00) 30.00     80.00    
  无 35 47 23 105(84.00) 33.33     78.10    
  肝转移           1.229 0.268   5.878 0.015
  有 5 8 9 22(17.60) 22.73     59.09    
  无 36 49 18 103(82.40) 34.95     82.52    
  PD-L1 TPS           1.960 0.162   1.816 0.178
  <1% 21 35 19 75(60.00) 28.00     74.67    
  ≥1% 20 22 8 50(40.00) 40.00     84.00    
外周血指标 NLR           2.088 0.148   12.468 0.001
  >3.25 13 19 19 51(40.80) 25.49     62.75    
  ≤3.25 28 38 8 74(59.20) 37.84     89.19    
  血红蛋白(g/L)           0.513 0.474   0.787 0.375
  <115 12 19 11 42(33.60) 28.57     73.81    
  ≥115 29 38 16 83(66.40) 34.94     80.72    
  C反应蛋白(mg/L)           1.155 0.282   1.384 0.240
  >8.50 13 22 13 48(38.40) 27.08     72.92    
  ≤8.50 28 35 14 77(61.60) 36.36     81.82    
  碱性磷酸酶(U/L)           0.368 0.544   0.140 0.708
  >95 11 18 9 38(30.40) 28.95     76.32    
  ≤95 30 39 18 87(69.60) 34.48     79.31    
  LDH(U/L)           2.227 0.136   10.867 0.001
  >225 11 17 17 45(36.00) 24.44     62.22    
  ≤225 30 40 10 80(64.00) 37.50     87.50    
  ALB(g/L)           0.394 0.530   6.935 0.008
  <36.52 10 12 13 35(28.00) 28.57     62.86    
  ≥36.52 31 45 14 90(72.00) 34.44     84.44    
  PLR           1.624 0.203   2.451 0.118
  >185.50 10 18 12 40(32.00) 25.00     70.00    
  ≤185.50 31 39 15 85(68.00) 36.47     82.35    
  LMR           0.941 0.332   1.290 0.256
  <2.65 12 20 12 44(35.20) 27.27     72.73    
  ≥2.65 29 37 15 81(64.80) 35.80     81.48    
表3 晚期NSCLC ICIs联合化疗PFS单因素及多因素Cox回归分析
影响因素 单变量分析 多变量分析
HR(95%CI) P值 HR(95%CI) P值
临床分期Ⅳ期 1.627(1.145~2.310) 0.007 1.253(0.821~1.914) 0.298
既往胸部放疗史 0.882(0.611~1.272) 0.495    
既往根治性手术史 0.820(0.550~1.276) 0.331    
肝转移 1.655(1.121~2.449) 0.012 1.524(1.032~2.248) 0.034
PD-L1 TPS<1% 1.540(1.090~2.178) 0.014 1.311(0.892~1.927) 0.173
NLR>3.25 2.216(1.523~3.212) 0.000 1.854(1.247~2.766) 0.003
血红蛋白<115 g/L 1.326(0.832~1.981) 0.183    
C但应蛋白>8.50 mg/L 1.682(1.151~2.454) 0.007 1.322(0.918~1.905) 0.133
碱性磷酸酶>95 U/L 1.253(0.855~1.846) 0.256    
LDH>225 U/L 1.981(1.367~2.881) 0.000 1.654(1.114~2.452) 0.013
ALB<36.52 g/L 1.581(1.083~2.315) 0.018 1.416(1.005~1.996) 0.046
PLR>185.50 1.385(0.927~2.078) 0.122    
LMR<2.65 1.422(0.951~2.125) 0.085    
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