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J Cancer 2017; 8(1):104-110. doi:10.7150/jca.16856 This issue Cite

Research Paper

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

Lin Wang¹, Chuanyong Wu¹, Lihua Qiao¹, Wenjun Yu¹, Qiaomei Guo¹, Mingna Zhao¹, Guohua Yang², Hang Zhao^3✉, Jiatao Lou^1✉

1. Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai 200030, China.
2. GenoSaber Biotech, 908 ziping Road, Bldg 26, Pudong, Shanghai, China.
3. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai 200030, China.

✉ Corresponding authors: Hang Zhao, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai 200030, China; Phone: 86-13701865603; Fax: 86-21-22200000-2908; E-mail: h_zhao28com; JiaTao Lou, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai 200030, China; Phone: 86-21-22200000-1601; Fax: 86-21-22200000-1601; E-mail: loujiataocom. More

Abstract

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.

Keywords: circulating tumor cells, folate receptor, ligand-targeted polymerase chain reaction, lung cancer.

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