背景与目的评价一种通过叶酸受体（folate receptor, FR）检测循环肿瘤细胞（circulating tumor cell, CTC）的方法用于肺癌临床诊断的实用性和可行性及进一步探究CTC在肺癌术后复发的预测价值。方法通过免疫磁珠负向富集方法从3 mL外周血中捕获循环肿瘤细胞，再用肿瘤特异性叶酸配体-寡核苷酸偶和物标记捕获的循环肿瘤细胞，洗去没有结合的偶和物后，洗脱下特异性结合的偶合物的寡核苷酸用于定量PCR扩增分析。结果97例肺癌患者的CTC水平高于肺部良性疾病患者（P<0.001）。本检测方法以8.7 Folate Units/3 mL为cutoff值，结果显示靶向PCR法对肺癌的检测灵敏度为82.5%，特异性为72.2%，特别是在I期肺癌灵敏度达到86.8%。与其他肿瘤标志物（NSE、CEA、CYFRA21-1）比较，CTC对肺癌及I期肺癌具有较高的诊断准确性（0.859；95%CI：0.779-0.939）和（0.912；95%CI：0.829-0.994）。5例肺癌患者术后2周内CTC水平高于cutoff值。结论叶酸受体阳性循环肿瘤细胞可以应用于肺癌的临床诊断，即使是对早期非小细胞肺癌（non-small cell lung cancer, NSCLC）的诊断。%Background and objective The aim of this study is to determine the effcacy and feasibility of a novel folate receptor (FR)-based circulating tumor cell (CTC) detection method in the diagnosis of lung cancer. CTCs were col-lected from 3 mL of blood based on negative enrichment by immunomagnetic beads and then labeled by a conjugate of a tumor-speciifc ligand folate and an oligonucleotide.Methods Atfer washing off redundant conjugates, the bound conjugates were removed and analyzed by quantitative polymerase chain reaction.Results The CTC levels of 97 patients with lung cancer were signiifcantly higher than that of the controls (18 patients with benign lung diseases;P<0.001). With a threshold of 8.7 Folate units, the method showed a sensitivity of 82.5% and a speciifcity of 72.2% in the diagnosis of lung cancer, especially a sensitivity of 86.8% in stage I disease. Compared with the existing clinical biomarkers such as neuron-speciifc enolase (NSE), carcinoembryonic antigen (CEA), and CYFAR21-1, the method showed the highest diagnostic effciency in lung cancer (area under the curve, 0.859; 95%CI: 0.779-0.939) and stage I lung cancer (area under the curve, 0.912; 95%CI: 0.829-0.994). For future work, the CTC levels of 5 lung cancer patients higher than 8.7 Folate units/3 mL in their postoperation.Conclusion FR-positive CTCs were feasible diagnostic biomarkers in patients with lung cancer, as well as in early-stage tumors.
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