Abstract
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.