[1]张杰,魏渼倬,赵玲,等.外周血中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值与接受免疫检查点抑制剂治疗食管鳞状细胞癌患者预后的相关性[J].新乡医学院学报,2023,40(7):621-627.[doi:10.7683/xxyxyxb.2023.07.004]
 ZHANG Jie,WEI Meizhuo,ZHAO Ling,et al.Correlation of neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio and the prognosis of esophageal squamous cell carcinoma treated with immune checkpoint inhibitors[J].Journal of Xinxiang Medical University,2023,40(7):621-627.[doi:10.7683/xxyxyxb.2023.07.004]
点击复制

外周血中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值与接受免疫检查点抑制剂治疗食管鳞状细胞癌患者预后的相关性
分享到:

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
40卷
期数:
2023年7
页码:
621-627
栏目:
临床研究
出版日期:
2023-07-05

文章信息/Info

Title:
Correlation of neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio and the prognosis of esophageal squamous cell carcinoma treated with immune checkpoint inhibitors
作者:
张杰12魏渼倬2赵玲2易善永2
(1.新乡医学院,河南 新乡 453003;2.郑州大学附属郑州中心医院肿瘤内科,河南 郑州  450007)
Author(s):
ZHANG Jie12WEI Meizhuo2ZHAO Ling2YI Shanyong2
(1.Xinxiang Medical University,Xinxiang 453003,Henan Province,China;2.Department of Oncology,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,Henan Province,China)
关键词:
食管鳞状细胞癌中性粒细胞与淋巴细胞数比值血小板与淋巴细胞比值免疫检查点抑制剂预后
Keywords:
esophageal squamous cell carcinomaneutrophil-to-lymphocyte ratioplatelet-to-lymphocyte ratioimmune checkpoint inhibitorprognosis
分类号:
R735.1
DOI:
10.7683/xxyxyxb.2023.07.004
文献标志码:
A
摘要:
目的 探讨外周血中性粒细胞与淋巴细胞比值(NLR)和血小板与淋巴细胞比值(PLR)与接受免疫检查点抑制剂(ICI)治疗的食管鳞状细胞癌(ESCC)预后的相关性。
方法 选择2020年3月至2022年5月在郑州大学附属郑州中心医院接受ICI治疗的59例ESCC患者为研究对象,患者接受ICI单药治疗或ICI联合化学治疗。收集患者的年龄、性别、美国东部肿瘤协作组评分、既往治疗方案、病理类型、TNM分期、远处转移等临床资料;分别于治疗前、治疗2个周期后,采集患者外周静脉血2 mL,应用BC-5180全自动血细胞分析仪检测患者的中性粒细胞计数、淋巴细胞计数、血小板计数,并计算NLR和PLR,ICI治疗前NLR、PLR以NLR0、PLR0表示,ICI治疗2个周期后NLR、PLR以NLR2、PLR2表示;每治疗2个周期后行实验室检查以及超声、CT、磁共振成像等影像学检查,参照实体瘤疗效评价标准1.1版评价疗效;患者随访至2022年6月30日,记录患者无进展生存期(PFS)。应用受试者操作特征(ROC)曲线分析NLR0、NLR2、PLR0和PLR2对ESCC疾病进展的评估价值,应用约登指数确定NLR、PLR的最佳截断值;应用Kaplan-Meier方法进行单因素生存分析,Cox回归模型进行多因素分析。
结果 59例ESCC患者中,完全缓解0例(0.0%),部分缓解13例(22.03%),疾病稳定15例(25.42%),疾病进展31例(52.55%)。NLR2预测ESCC疾病进展的曲线下面积(AUC)为0.610(P>0.05)。NLR0预测ESCC疾病进展的AUC为0.697[95%置信区间(CI):0.560~0.834,P=0.005],灵敏度为67.7%,特异度为75.0%,最佳截断值为3.00;PLR0预测ESCC疾病进展的AUC为0.740(95%CI:0.614~0.866,P<0.001),灵敏度为58.1%,特异度为82.1%,最佳截断值为187.75;PLR2预测ESCC疾病进展的AUC为0.724(95%CI:0.592~0.855,P=0.001),灵敏度为83.9%,特异度为60.7%,最佳截断值为152.21。高NLR0组Ⅳ期患者占比显著高于低NLR0组,高PLR0组Ⅳ期患者占比显著高于低PLR0组,高PLR2组Ⅳ期患者占比显著高于低PLR2组(P<0.05);高NLR0组远处转移的比例显著高于低NLR0组(P<0.05);不同水平NLR0、PLR0、PLR2组患者的年龄、性别、手术、淋巴结转移、治疗方式比较差异均无统计学意义(P>0.05)。59例患者的总体中位PFS为9.33个月(95%CI:6.104~12.553)。低NLR0组患者的中位PFS显著长于高NLR0组,低PLR0组患者的中位PFS显著长于高PLR0组,低PLR2组患者的中位PFS显著长于高NLR2组(P<0.05);Ⅱ期、Ⅲ期患者的中位PFS显著长于Ⅳ期患者(P<0.05);无远处转移患者的中位PFS显著长于远处转移患者(P<0.05)。患者的年龄、性别、手术、淋巴结转移及治疗方式与患者的PFS无相关性(P>0.05)。NLR0、PLR2、远处转移是影响ESCC患者PFS的独立预测因素(P<0.05),PLR0对ESCC患者的PFS无预测价值(P>0.05)。
结论 ESCC患者的外周血NLR、PLR与ICI治疗预后相关,高NLR0、PLR0和PLR2水平的ESCC患者可能较难从ICI治疗中获益,且NLR0与PLR2可作为评估ESCC患者PFS的独立预测指标。
Abstract:
Objective To explore the correlation of neutrophil-to-lymphocyte ratio(NLR) and platelet-to-lymphocyte ratio(PLR) with the prognosis of esophageal squamous cell carcinoma(ESCC) treated with immune checkpoint inhibitor(ICI).
Methods A total of 59 ESCC patients who received ICI treatment at Zhengzhou Central Hospital Affiliated to Zhengzhou University from March 2020 to May 2022 were selected as the research subjects,the patients received either ICI monotherapy or ICI combined chemotherapy.The clinical data of patients including age,gender,Eastern Cooperative Oncology Group score,previous treatment regimen,pathological type,TNM stage,and distant metastasis were collected.Before treatment and after 2 cycles of treatment,2 mL peripheral venous blood was collected from the patients,and the neutrophil count,lymphocyte count,and platelet count of the patients were detected by BC-5180 automatic blood cell analyzer,the NLR and PLR were calculated.NLR and PLR before ICI treatment were expressed as NLR0 and PLR0,NLR and PLR after 2 cycles of ICI treatment were expressed as NLR2 and PLR2.After every 2 cycles of treatment,laboratory tests,ultrasound,CT,magnetic resonance imaging and other imaging examinations were performed to evaluate the efficacy according to response evaluation criteria in solid tumors 1.1.The patients were followed up to June 30,2022,and the progression-free survival(PFS) of the patients was recorded.The value of NLR0,NLR2,PLR0 and PLR2 in evaluating the progression of ESCC was analyzed by receiver operating characteristic(ROC) curve,and the best cut-off value of NLR and PLR was determined by Youden index.Kaplan-Meier method was used for univariate survival analysis,and Cox regression model was used for multivariate analysis.
Results Among the 59 ESCC patients,there were no cases of complete response,13 cases of partial response(22.03%),15 cases of stable disease (25.42%),and 31 cases of progressive disease(52.55%).The area under the curve(AUC) of NLR2 in predicting the progression of ESCC was 0.610(P>0.05).The AUC of NLR0 in predicting the progression of ESCC was 0.697[95% confidence interval (CI):0.560-0.834,P=0.005],the sensitivity was 67.7%,the specificity was 75.0%,and the best cut-off value was 3.00.The AUC of PLR0 in predicting the progression of ESCC was 0.740(95%CI:0.614-0.866,P<0.001),the sensitivity was 58.1%,the specificity was 82.1%,and the best cut-off value was 187.75.The AUC of PLR2 in predicting the progression of ESCC was 0.724(95%CI:0.592-0.855,P=0.001),the sensitivity was 83.9%,the specificity was 60.7%,and the best cut-off value was 152.21.The proportion of stage Ⅳ patients in the high NLR0 group was significantly higher than that in the low NLR0 group,the proportion of stage Ⅳ patients in the high PLR0 group was significantly higher than that in the low PLR0 group,and the proportion of stage Ⅳ patients in the high PLR2 group was significantly higher than that in the low PLR2 group(P<0.05).The proportion of distant metastases in the high NLR0 group was significantly higher than that in the low NLR0 group(P<0.05).There were no significant differences in age,gender,surgery,lymph node metastasis and treatment methods among patients with different levels of NLR0,PLR0 and PLR2(P>0.05).The overall median PFS of 59 patients was 9.33 months(95%CI:6.104-12.553).The median PFS of patients in the low NLR0 group was significantly longer than that in the high NLR0 group,the median PFS of patients in the low PLR0 group was significantly longer than that in the high PLR0 group,the median PFS of patients in the low PLR2 group was significantly longer than that in the high NLR2 group(P<0.05);the median PFS of patients in stage Ⅱ and Ⅲ was significantly longer than that in stage Ⅳ(P<0.05);the median PFS of patients without distant metastasis was significantly longer than that of patients with distant metastasis(P<0.05).Age,gender,surgery,lymph node metastasis and treatment modality did not correlate with PFS(P>0.05).NLR0,PLR2 and distant metastasis were independent predictors of PFS in patients with ESCC(P<0.05),and PLR0 had no predictive value for PFS in patients with ESCC(P>0.05).
Conclusion The peripheral blood NLR and PLR levels are related to the prognosis of ESCC patients treated with ICI.ESCC patients with high levels of NLR0,PLR0 and PLR2 may be less likely to benefit from ICI treatment,NLR0 and PLR2 can be used as independent predictors for PFS of ESCC patients.

参考文献/References:

[1] SIEGEL R L,MILLER K D,FUCHS H E,et al.Cancer statistics,2022[J].CA Cancer J Clin,2022,72(1):7-33.
[2] SINGH N,BABY D,RAJGURU J P,et al.Inflammation and cancer[J].Ann Afr Med,2019,18(3):121-126.
[3] TAN Q,LIU S,LIANG C,et al.Pretreatment hematological markers predict clinical outcome in cancer patients receiving immune checkpoint inhibitors:a meta-analysis[J].Thoracic Cancer,2018,9(10):1220-1230.
[4] ZHANG X,WANG Y,ZHAO L,et al.Prognostic value of platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer:a systematic review and meta-analysis[J].Int J Biol Markers,2018,33(4):335-344.
[5] 中华人民共和国国家卫生健康委员会医政医管局.食管癌诊疗指南(2022年版)[J].中华消化外科杂志,2022,21(10):1247-1268.
BUREAU OF MEDICAL ADMINISTRATION,NATIONAL HEALTH COMMISSION OF THE PEOPLE′S PRPUBLIC OF CHINA.Standardization for diagnosis and treatment of esophageal cancer(2022 edition)[J].Chin J Digest Surg,2022,21(10):1247-1268.
[6] EISENHAUER E A,THERASSE P,BOGAERTS J,et al.New response evaluation criteria in solid tumours:revised RECIST guideline (version 1.1)[J].Eur J Cancer,2009,45(2):228-247.
[7] LUO H,LU J,BAI Y,et al.Effect of camrelizumab vs placebo added to chemotherapy on survival and progression-free survival in patients with advanced or metastatic esophageal squamous cell carcinoma:the ESCORT-1st randomized clinical trial[J].JAMA,2021,326(10):916-925.
[8] XU X,JING J.Inflammation-related parameter serve as prognostic biomarker in esophageal squamous cell carcinoma[J].Front Oncol,2022,12:900305.
[9] KROESE T E,DIJKSTERHUIS W P M,VAN ROSSUM P,et al.Prognosis of interval distant metastases after neoadjuvant chemoradiotherapy for esophageal cancer[J].Ann Thorac Surg,2022,113(2):482-490.
[10] ARNETH B.Tumor microenvironment[J].Medicina(Kaunas),2019,56(1):15.
[11] LV B,WANG Y,MA D,et al.Immunotherapy:reshape the tumor immune microenvironment[J].Front Immunol,2022,13:844142.
[12] ZHANG X,GARI A,LI M,et al.Combining serum inflammation indexes at baseline and post treatment could predict pathological efficacy to anti PD 1 combined with neoadjuvant chemotherapy in esophageal squamous cell carcinoma[J].J Transl Med,2022,20(1):16.
[13] WANG W,TONG Y,SUN S,et al.Predictive value of NLR and PLR in response to preoperative chemotherapy and prognosis in locally advanced gastric cancer[J].Front Oncol,2022,12:936206.
[14] LOU C,JIN F,ZHAO Q,et al.Correlation of serum NLR,PLR and HALP with efficacy of neoadjuvant chemotherapy and prognosis of triple-negative breast cancer[J].Am J Transl Res,2022,14(5):3240-3246.
[15] LIU N,MAO J,TAO P,et al.The relationship between NLR/PLR/LMR levels and survival prognosis in patients with non-small cell lung carcinoma treated with immune checkpoint inhibitors[J].Medicine(Baltimore),2022,101(3):e28617.
[16] TEMPLETON A J,MCNAMARA M G,ERUGA B,et al.Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors:a systematic review and meta-analysis[J].J Nat Cancer Inst,2014,106(6):dju124.
[17] DIEM S,SCHMID S,KRAPF M,et al.Neutrophil-to-lymphocyte ratio(NLR) and platelet-to-lymphocyte ratio(PLR) as prognostic markers in patients with non-small cell lung cancer(NSCLC) treated with nivolumab[J].Lung Cancer,2017,111:176-181.
[18] KUTLU Y,AYDIN S G,BILICI A,et al.Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as prognostic markers in patients with extensive-stage small cell lung cancer treated with atezolizumab in combination with chemotherapy[J].Medicine(Baltimore),2023,102(15):e33432.
[19] GOU M,QU T,WANG Z,et al.Neutrophil-to-lymphocyte ratio (NLR) predicts PD-1 inhibitor survival in patients with metastatic gastric cancer[J].J Immunol Res,2021,2021:2549295.
[20] SUN Y,ZHANG L.The clinical use of pretreatment NLR,PLR,and LMR in patients with esophageal squamous cell carcinoma:evidence from a meta-analysis[J].Cancer Manag Res,2018,10:6167-6179.
[21] JAILLON S,PONZETTA A,DI MITRI D,et al.Neutrophil diversity and plasticity in tumour progression and therapy[J].Nat Rev Cancer,2020,20(9):485-503.
[22] XIONG S,DONG L,CHENG L.Neutrophils in cancer carcinogenesis and metastasis[J].J Hematol Oncol,2021,14(1):173.
[23] LIU Y,ZHANG Y,DING Y,et al.Platelet-mediated tumor metastasis mechanism and the role of cell adhesion molecules[J].Crit Rev Oncol Hematol,2021,167:103502.
[24] D′AMBROSI S,NILSSON R J,Wurdinger T.Platelets and tumor-associated RNA transfer[J].Blood,2021,137(23):3181-3191.
[25] WU X,HAN R,ZHONG Y,et al.Post treatment NLR is a predictor of response to immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma[J].Cancer Cell Int,2021,21(1):356.
[26] LIU J,LI S,ZHANG S,et al.Systemic immune-inflammation index,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio can predict clinical outcomes in patients with metastatic non-small-cell lung cancer treated with nivolumab[J].J Clin Lab Anal,2019,33(8):e22964.
[27] YODYING H,MATSUDA A,MIYASHITA M,et al.Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer:a systematic review and meta-analysis[J].Ann Surg Oncol,2016,23(2):646-654.

相似文献/References:

[1]李陕区,赵仁礼,巩 丽,等.酪氨酸蛋白磷酸酶样A 结构域2在食管鳞状细胞癌组织中的表达及其临床意义[J].新乡医学院学报,2014,31(11):906.[doi:10.7683/xxyxyxb.2014.11.011]
[2]齐 博,赵宝生,李汉臣,等.角化细胞生长因子在食管鳞状细胞癌中的表达[J].新乡医学院学报,2015,32(05):401.
[3]李东峰1,徐慧萍1,王忠民2.基质金属蛋白酶2在食管鳞状细胞癌中的表达[J].新乡医学院学报,2015,32(09):839.
[4]张惠娟,赵学科,宋 昕,等.食管鳞状细胞癌组织中PLCE1蛋白表达与患者生存的关系[J].新乡医学院学报,2017,34(12):1068.[doi:10.7683/xxyxyxb.2017.12.006]
 ZHANG Hui-juan,ZHAO Xue-ke,SONG Xin,et al.Expression of PLCE1 in esophageal squamous cell carcinoma tissues and survival analysis[J].Journal of Xinxiang Medical University,2017,34(7):1068.[doi:10.7683/xxyxyxb.2017.12.006]
[5]王 淼,曹克鑫,陈志军,等.食管鳞状细胞癌组织中plexin-A4和程序性死亡蛋白-1表达与预后的关系[J].新乡医学院学报,2021,38(7):666.[doi:10.7683/xxyxyxb.2021.07.014]
 WANG Miao,CAO Kexin,CHEN Zhijun,et al.Expression of plexin-A4 and programmed death-1 in esophageal squamous cell carcinoma and their relationship with prognosis[J].Journal of Xinxiang Medical University,2021,38(7):666.[doi:10.7683/xxyxyxb.2021.07.014]
[6]刘艳娇,张兴隆,何龙英,等.细胞分裂周期蛋白20、拓扑异构酶ⅡA、有丝分裂相关激酶2的表达与食管鳞状细胞癌患者临床病理特征的相关性[J].新乡医学院学报,2021,38(12):1137.[doi:10.7683/xxyxyxb.2021.12.006]
 LIU Yanjiao,ZHANG Xinglong,HE Longying,et al.Correlation between the expression of cell division cycle 20,topoisomerase ⅡA,NIMA-related kinase 2 and clinicopathological characteristics of patients with esophageal squamous cell carcinoma[J].Journal of Xinxiang Medical University,2021,38(7):1137.[doi:10.7683/xxyxyxb.2021.12.006]
[7]任利兵,贾如江,苏春永,等.食管鳞状细胞癌组织中miR-504和磷脂酰肌醇3-激酶/蛋白激酶B通路相关分子表达及其与患者临床病理学特征的关系[J].新乡医学院学报,2020,37(9):839.[doi:10.7683/xxyxyxb.2020.09.007]
 REN Libing,JIA Rujiang,SU Chunyong,et al.Expression of miR-504 and phosphatidylinositol 3-kinase/protein kinase B pathway related molecules in esophageal squamous cell carcinoma and the relationship between them with the clinicopathological feature of patients[J].Journal of Xinxiang Medical University,2020,37(7):839.[doi:10.7683/xxyxyxb.2020.09.007]
[8]贺家勇,徐 茜,杨晨晨.微小RNA-26a对食管癌Eca109细胞增殖、迁移、凋亡及细胞周期的影响[J].新乡医学院学报,2019,36(2):131.[doi:10.7683/xxyxyxb.2019.02.007]
 HE Jia-yong,XU Qian,YANG Chen-chen.Influence of microRNA-26a on the proliferation,migration,apoptosis and cell cycle of esophageal cancer cells Eca109[J].Journal of Xinxiang Medical University,2019,36(7):131.[doi:10.7683/xxyxyxb.2019.02.007]
[9]董起杭,万里新,张 凯,等.安罗替尼联合放射治疗对食管鳞状细胞癌细胞增殖、凋亡及放射治疗敏感性的影响[J].新乡医学院学报,2022,39(2):106.[doi:10.7683/xxyxyxb.2022.02.002]
 DONG Qihang,WAN Lixin,ZHANG Kai,et al.Effect of anlotinib combined with radiotherapy on the proliferation,apoptosis and radiotherapy sensitivity of esophageal squamous cell carcinoma cells[J].Journal of Xinxiang Medical University,2022,39(7):106.[doi:10.7683/xxyxyxb.2022.02.002]
[10]肖怀葱,张彩凤,赵润根,等.中性粒细胞淋巴细胞比、环氧合酶-2及核转录因子-κB在食管鳞状细胞癌中表达的意义[J].新乡医学院学报,2017,34(3):184.[doi:10.7683/xxyxyxb.2017.03.007]
 XIAO Huai-cong,ZHANG Cai-feng,ZHAO Run-gen,et al.Expression of neutrophil to lymphcyte ratio,cyclooxygenase-2 and nuclear factor kappa B in esophageal squamous carcinoma[J].Journal of Xinxiang Medical University,2017,34(7):184.[doi:10.7683/xxyxyxb.2017.03.007]

更新日期/Last Update: 2023-07-05