循环肿瘤细胞和循环肿瘤脱氧核糖核酸检测在预测晚期非小细胞肺癌免疫治疗效果中的应用研究  

Study on the application of circulating tumor cell and circulating tumor deoxyribonucleic acid detection in predicting the effect of immunotherapy for advanced non-small cell lung carcinoma

作　　者：张静[1] 纪灏[2] 李志夫[3] Zhang Jing;Ji Hao;Li Zhifu(Department of Infection,Shanghai Chest Hospital,Shanghai 200030,China;Department of Respiratory Medicine,Shanghai Chest Hospital,Shanghai 200030,China;Clinical Lab,Shanghai Chest Hospital,Shanghai 200030,China)

机构地区：[1]上海市胸科医院感染科,上海200030 [2]上海市胸科医院呼吸内科,上海200030 [3]上海市胸科医院检验科,上海200030

出　　处：《中国医学前沿杂志（电子版）》2020年第10期109-113,共5页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

摘　　要：目的探讨循环肿瘤细胞(circulating tumor cell,CTC)和循环肿瘤脱氧核糖核酸(circulating tumor deoxyrib onu cleic acid,ctDNA)检测在预测晚期非小细胞肺癌(non-small cell lung carcinoma,NSCLC)免疫治疗效果中的应用价值。方法选取2016年2月至2017年2月上海市胸科医院收治的接受免疫治疗的79例晚期NSCLC患者为研究对象,采集患者治疗前后空腹静脉血,采用免疫磁珠法和免疫荧光染色法检测CTC数目,采用杂交捕获高通量测序检测外周血ctDNA的单核苷酸变异,分析CTC数目、ctDNA基因突变与免疫治疗效果和无进展生存(progress free survive,PFS)时间的关系。结果79例晚期NSCLC患者中有54例检测到CTC,阳性率为68.35%,每4 ml外周血含有的中位CTC数目为4个(0~53个)。Ⅳ期NSCLC患者CTC阳性率显著高于Ⅲ期NSCLC患者(P<0.05),免疫治疗后CTC阳性率显著低于免疫治疗前(P<0.05)。按照实体肿瘤疗效评价标准1.1,部分缓解23例,疾病稳定46例,疾病进展10例;部分缓解患者中,CTC数目升高2例,不变9例,降低12例;ctDNA基因变异数<2为24例,变异数≥2为55例。Spearman相关性分析显示CTC数目变化和ctDNA基因变异数与免疫治疗效果均呈显著负相关(均P<0.05)。基线期CTC阴性组与阳性组患者、ctDNA基因变异数<2组与≥2组患者PFS时间比较差异均有统计学意义(均P<0.05)。结论CTC和ctDNA基因突变与晚期NSCLC患者肿瘤转移相关,外周血CTC和ctDNA检测对接受免疫治疗的晚期NSCLC患者的治疗效果和预后可能具有一定的预测价值。Objective To explore the application of circulating tumor cell(CTC)and circulating tumor deoxyribonucleic acid(ctDNA)detection in predicting the effect of immunotherapy for advanced non-small cell lung carcinoma(NSCLC).Method Seventynine patients with advanced NSCLC who received immunotherapy in Shanghai Chest Hospital from February 2016 to February 2017 were selected as subjects,fasting venous blood was collected before and after treatment.The number of CTC was detected by immunomagnetic beads and immunofluorescence staining,detection of single nucleotide variation in peripheral blood ctDNA by hybridization capture high-throughput sequencing,the relationship between the number of CTC,the gene mutation of ctDNA and the effect of immunotherapy and the time of progress free survive(PFS)was analyzed.Result The positive rate of CTC was 68.35%(54/79),the median number of CTC in every 4 ml of peripheral blood was 4(0~53).The positive rate of CTC in patients with stageⅣNSCLC was significantly higher than that in patients with stageⅢNSCLC(P<0.05),the positive rate of CTC after immunotherapy was significantly lower than that before immunotherapy(P<0.05).According to the response evaluation criteria in solid tumor(RECIST)1.1,there were 23 cases of partial remission,46 cases of stable disease and 10 cases of progressive disease,among the partial remission patients,the number of CTC increased in 2 cases,unchanged in 9 cases and decreased in 12 cases;the number of ctDNA gene variants<2 was found in 24 cases,and the number of variants≥2 was found in 55 cases.Spearman correlation analysis showed that the number of CTC and ctDNA gene mutations were negatively correlated with the effect of immunotherapy(all P<0.05).There were significant differences in PFS time between CTC negative group and positive group,and between ctDNA gene mutation<2 group and≥2 group at baseline(all P<005).Conclusion CTC and ctDNA gene mutations are associated with tumor metastasis in patients with advanced NSCLC.Detection of CTC and ctDNA in perip

关 键 词：循环肿瘤细胞 循环肿瘤脱氧核糖核酸 非小细胞肺癌 免疫治疗 

分 类 号：R734.2[医药卫生—肿瘤]