Clinical Significance of Folate Receptor-positive Circulating Tumor Cells Detected by Ligand-targeted Polymerase Chain Reaction in Lung Cancer

Background: As the heterogeneity of CTCs is becoming increasingly better understood, it is clear that identifying particular subtypes of CTCs would be more relevant. Methods: We detected folate receptor (FR)-positive circulating tumor cells (FR(+)-CTCs) by a novel ligand-targeted polymerase chain reaction (LT-PCR) detection technique. Results: In the none-dynamic study, FR(+)-CTC levels of patients with lung cancer were significantly higher than controls (patients with benign lung diseases and healthy controls). With a threshold of 8.7 CTC units, FR(+)-CTC showed a sensitivity of 77.7% and specificity of 89.5% in the diagnosis of lung cancer. When compared with established clinical biomarkers including carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and neuron-specific enolase (NSE), FR(+)-CTC showed the highest diagnostic efficiency. Notably, the combination of FR(+)-CTC, CEA, NSE, and CYFRA21-1 could significantly improve the diagnostic efficacy in differentiating patients with lung cancer from benign lung disease. In our dynamic surveillance study, the CTC levels of 62 non-small cell lung cancer (NSCLC) patients decreased significantly after tumor resection. Conclusion: We established a LT-PCR-based FR(+)-CTC detection platform for patients with lung cancer that exhibits high sensitivity and specificity. This platform would be clinical useful in lung cancer diagnosis and treatment response assessment.