特异性循环肺癌细胞流式检测参考区间的建立及在非小细胞肺癌化疗中的应用

Establishment of the reference intervals of specific circulating lung cancer cell and its application on non-small cell lung cancer chemotherapy

目的建立特异性循环肺癌细胞（SCLCC）流式检测的参考区间并探讨在非小细胞肺癌（NSCLC）化疗前后的应用。方法采用病例对照研究方法，对2013年11月至2014年5月南京医科大学第一附属医院130名体检合格人员外周血进行SCLCC水平检测，建立SCLCC的参考区间。对2013年10月至2014年6月南京医科大学第一附属医院收治的70例确诊NSLCC患者化疗前后SCLCC水平、癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）和角质蛋白19片段（CYFRA21—1）进行检测，同时行胸部CT检查，采用配对秩和检验进行分析。结果健康人外周血SCLCC的参考区间为0～504个／ml；70例NSCLC患者化疗前SCLCC水平为673（43～2876）个／ml，显著高于化疗后456（14～2288）个／ml，差异有统计学意义（Z=-4．65，P〈0．01）；其中17例部分缓解患者SCLCC水平从1109（225～2729）个／ml显著降低至453（101～988）个／ml（Z=-3．53，P〈0．01），而35例疾病稳定患者SCLCC水平从773（84～2354）个／ml降低至540（102～2288）个／ml，降低水平不明显（Z=-1．79，P=0．073）。结论SCLCC流式检测技术在对NSCLC的治疗评价中具有重要的临床价值。

Objective To establish the biological reference interval of specific circulating lung cancer cell（SCLCC） and evaluate its clinical value in non-small cell lung cancer（ NSCLC ） chemotherapy. Methods The biological reference interval of peripheral blood SCLCC was established by detecting the levels of SCLCC in 130 healthy individuals from the First Affiliated Hospital of Nanjing Medical University from November 2013 to May 2014 by flow cytometry. On basis of detecting the SCLCC ,a case-control study was conducted. SCLCC, carcino-embryonic antigen（CEA）, neuronspecific enolase（NSE） and CYFRA21-1 were measured in 70 cases of NSCLC patients collected from October 2013 to June 2014 before and after chemotherapy, meanwhile, CT scan was performed. Wilcoxon rank sum test was used for the analysis. Results The reference interval of SCLCC for the healthy population was （0 -504 ）/ml. After chemotherapy, the levels of SCLCC were decreased from 673 （43 - 2 876 ）/ml to 456 （ 14 - 2 288 ）/ml in 70 NSCLC patients（ Z = - 4. 65, P 〈 0. 01 ）, among which SCLCC were significantly decreased in 17 partial response patients from 1 109（225 -2 729）/ml to 453（ 101 -988）/ml （Z = -3.53,P 〈0. 01）. However, SCLCC decreased from 773 （ 84 - 2 354）/ml to 540 （ 102 - 2 288 ）/ml in 35 stable disease patients （ Z = -1.79 ,P = 0. 073） which was not statistically significant. Conclusion Determination of SCLCC by flow cytometry has great clinical value in the treatment evaluation in NSCLC.