Background: The aim of this study is to determine the efficacy and feasibility of a novel folate receptor (FR)-based circulating tumor cell (CTC) detection method in the diagnosis of lung cancer. CTCs were collected from 3 mL of blood based on negative enrichment by immunomagnetic beads and then labeled by a conjugate of a tumor-specific ligand folate and an oligonucleotide.
Methods: After 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 significantly 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 specificity 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-specific enolase (NSE), carcinoembryonic antigen (CEA), and CYFRA21-1, the method showed the highest diagnostic efficiency 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.
Conclusions: FR-positive CTCs were feasible diagnostic biomarkers in patients with lung cancer, as well as in early-stage tumors.
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。.