晚期NSCLC患者外周血循环肿瘤细胞水平与疗效相关性及其临床意义-东南大学学报医学版

晚期NSCLC患者外周血循环肿瘤细胞水平与疗效相关性及其临床意义

单位：1. 沧州市人民医院输血科, 河北沧州 061001;
2. 邯郸市中心医院肿瘤三科, 河北邯郸 056000

分类号：R734.2

出版年·卷·期（页码）：2026·45·第一期（91-97）

摘要：

目的:探讨晚期非小细胞肺癌(NSCLC)患者程序性死亡受体1(PD-1)抑制剂治疗前后外周血循环肿瘤细胞(CTCs)水平变化,并分析其对治疗效果的预测价值。方法:选取2020年5月至2024年5月本院125例晚期NSCLC患者,均行PD-1抑制剂治疗,依据治疗效果分为有效组和无效组,比较其临床资料及治疗前后CTCs水平,分析疗效的影响因素。观察CTCs对疗效的预测价值及其与治疗后无效风险关联强度。评价CTCs对治疗后无效的临床效用性。结果:无效患者吸烟史、临床分期Ⅳ期所占比例及治疗1、2个周期CTCs明显高于有效患者(均P＜0.05);吸烟史、临床分期及治疗1、2个周期CTCs均为晚期NSCLC患者PD-1抑制剂治疗后无效的危险因素(均P＜0.05);治疗1、2个周期CTCs预测晚期NSCLC患者PD-1抑制剂治疗后无效的最佳截断值分别为2.08、1.37 FR·mL^-1,AUC值分别为0.764、0.751;治疗1、2个周期CTCs连续变化与晚期NSCLC患者PD-1抑制剂治疗后无效风险关联强度呈非线性剂量反应关系(均P＜0.05);治疗1、2个周期CTCs连续变化与晚期NSCLC患者PD-1抑制剂治疗后无效风险呈正相关;在阈值0.2~0.9时,治疗2个周期CTCs对预测晚期NSCLC患者PD-1抑制剂患者治疗后无效风险具有一定价值。结论:晚期NSCLC患者CTCs明显升高与PD-1抑制剂患者治疗后无效呈正相关,其对晚期NSCLC患者PD-1抑制剂治疗后无效风险具有一定预测价值。

Objective: To investigate the changes in the levels of circulating tumor cells(CTCs) in peripheral blood of patients with advanced non-small cell lung cancer(NSCLC) before and after treatment with programmed death receptor 1(PD-1) inhibitors, and analyze its predictive value for therapeutic efficacy. Methods: A total of 125 patients with advanced NSCLC from May 2020 to May 2024 were selected. All patients were treated with PD-1 inhibitors. According to the therapeutic effect, they were divided into effective and ineffective groups, and their clinical data and CTCs before and after treatment were compared. The influencing factors of therapeutic efficacy were analyzed. The predictive value of CTCs on the efficacy and its correlation with the risk of treatment failure after treatment were observed. The clinical utility of CTCs for treatment failure was evaluated. Results: The proportion of smoking history, clinical stage IV and CTCs in 1 and 2 cycles of treatment in ineffective patients were significantly higher than those in effective patients(all P<0.05). Smoking history, clinical stage and CTCs in 1 and 2 cycles of treatment were all risk factors for ineffective PD-1 inhibitor treatment in patients with advanced NSCLC(all P<0.05). The optimal cut-off values of CTCs for predicting ineffective PD-1 inhibitor treatment in patients with advanced NSCLC after 1 and 2 cycles of treatment were 2.08 and 1.37 FR·mL^-1, respectively, and area under the curve(AUC) values were 0.764 and 0.751, respectively. There was a non-linear dose-response relationship between the continuous changes of CTCs in 1 and 2 cycles of treatment and the risk of ineffective PD-1 inhibitor treatment in patients with advanced NSCLC(all P<0.05). The continuous changes of CTCs after 1 and 2 cycles of treatment were positively correlated with the risk of PD-1 inhibitor failure in patients with advanced NSCLC. When the threshold was 0.2-0.9, CTCs after 2 cycles of treatment had a certain value in predicting the risk of treatment failure of PD-1 inhibitors in patients with advanced NSCLC. Conclusion: The significant increase of CTCs in patients with advanced NSCLC is positively correlated with the ineffectiveness of PD-1 inhibitors after treatment, which has a certain predictive value for the risk of treatment failure with PD-1 inhibitors.

参考文献：

[1] YU D,YANG P,LU X,et al.Single-cell RNA sequencing reveals enhanced antitumor immunity after combined application of PD-1 inhibitor and Shenmai injection in non-small cell lung cancer[J].Cell Commun Signal,2023,21(1):169.
[2] ZHENG L,HU F,HUANG L,et al.Association of metabolomics with PD-1 inhibitor plus chemotherapy outcomes in patients with advanced non-small-cell lung cancer[J].J Immunother Cancer,2024,12(4):e008190.
[3] CHO J W,HONG M H,HA S J,et al.Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer[J].Exp Mol Med,2020,52(9):1550-1563.
[4] CHEN Y,WEN S,XIA J,et al.Association of dynamic changes in peripheral blood indexes with response to PD-1 inhibitor-based combination therapy and survival among patients with advanced non-small cell lung cancer[J].Front Immunol,2021,12:672271.
[5] 马竹青,王瑞芳,姜陵,等.外周血循环肿瘤细胞与宫颈癌临床病理特征的关系及对疾病复发的评估价值[J].实用癌症杂志,2025,40(3):390-393.
[6] SMIT D J,PANTEL K,JÜCKER M.Circulating tumor cells as a promising target for individualized drug susceptibility tests in cancer therapy[J].Biochem Pharmacol,2021,188:114589.
[7] 中华医学会,中华医学会肿瘤学分会,中华医学会杂志社,等.中华医学会肺癌临床诊疗指南(2018版)[J].中华肿瘤杂志,2018,40(12):935-964.
[8] 吕厚宽,庄文辉,黄一桂,等.PD-1/PD-L1抑制剂治疗非小细胞肺癌的疗效及预后观察[J].癌症进展,2020,18(3):279-281.
[9] 张雯,邱欢,魏贤,等.肺癌患者VATS术后运动恐惧与疼痛应对策略的潜在剖面分析[J].现代医学,2025,53(8):1239-1247.
[10] SAKAMOTO M,JIMENO A.Sugemalimab,a novel PD-L1 inhibitor for treatment of advanced ormetastatic non-small cell lung cancer[J].Drugs Today,2023,59(3):169-177.
[11] LA-BECK N M,NGUYEN D T,LE A D,et al.Optimizing patient outcomes with PD-1/PD-L1 immune checkpoint inhibitors for the first-line treatment of advanced non-small cell lung cancer[J].Pharmacother J Hum Pharmacol Drug Ther,2020,40(3):239-255.
[12] RAZA A,MOHSEN R,KANBOUR A,et al.Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression[J].Front Immunol,2023,14:1157100.
[13] RUPP B,BALL H,WUCHU F,et al.Circulating tumor cells in precision medicine:challenges and opportunities[J].Trends Pharmacol Sci,2022,43(5):378-391.
[14] GAO F,ZHAO W,LI M,et al.Role of circulating tumor cell detection in differentiating tumor recurrence from treatment necrosis of brain gliomas[J].BioScience Trends,2021,15(2):107-117.
[15] HUSSAIN S H,HUERTAS C S,MITCHELL A,et al.Biosensors for circulating tumor cells(CTCs)-biomarker detection in lung and prostate cancer:trends and prospects[J].Biosens Bioelectron,2022,197:113770.
[16] VAFAEI S,ROUDI R,MADJD Z,et al.Potential theranostics of circulating tumor cells and tumor-derived exosomes application in colorectal cancer[J].Cancer Cell Int,2020,20(1):288.
[17] 冯雨,崔东,张会民,等.外周血循环肿瘤细胞联合血清肿瘤标志物检测在非小细胞肺癌患者中的临床意义[J].实用医院临床杂志,2022,19(6):31-33.
[18] 王亚东,杨笑盈,贾梓淇,等.循环肿瘤细胞PD-L1表达在非小细胞肺癌免疫治疗中的应用[J].中国胸心血管外科临床杂志,2021,28(1):110-115.
[19] 杨学文,肖书傲,刘书尚,等.细胞角蛋白19片段抗原21-1和循环肿瘤细胞检测对晚期食管癌化疗效果及预后生存的评估作用[J].临床误诊误治,2021,34(10):44-47,53.
[20] 刘霞,董丽娟,张军鹏,等.循环肿瘤细胞在胃癌临床分期判断、疗效监测及预后评估中的价值[J].海南医学,2020,31(22):2915-2918.
[21] LIN D,SHEN L,LUO M,et al.Circulating tumor cells:biology and clinical significance[J].Signal Transduct Target Ther,2021,6:404.
[22] 邱文瀚,李一渊,吴汝基,等.外周血循环肿瘤细胞在评估转移性前列腺癌患者多西他赛化疗疗效及预测预后中的应用研究[J].中华泌尿外科杂志,2020,41(1):60-64.
[23] 郑庆凯,程文静,郑红,等.肺癌患者外周血循环肿瘤细胞与肿瘤转移及新辅助化疗疗效的关系[J].癌症进展,2024,22(17):1943-1946.
[24] 李晓华,李洁,唐军伟.外周血循环肿瘤细胞和肿瘤标志物在评估老年非小细胞肺癌患者化疗后疗效中的价值[J].河北医学,2021,27(5):779-785.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录