The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

Abstract

Objective: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer.

Method: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by the SE i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18.

Results: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752-0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, subsolid nodules and nodules ≥8 mm.

Conclusions: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, subsolid nodules and nodules ≥8 mm.

Keywords: CEA; Circulating tumour cells; Lung cancer; Management; Solitary pulmonary nodules.

Fig. 1

CTC counts in patients with SPNs. (A). CTC counts between patients with benign lung diseases and those with NSCLC. (B). CTC counts in patients with nodules in the upper lobe of the lung and other sites. (C). CTC counts in patients with NSCLC aged < 60 years and ≥ 60 years. (D) CTC counts in patients with NSCLC with MTD < 8 mm and those with MTD ≥8 mm. (E). CTC counts in male and female patients with NSCLC. (F). CTC counts in patients with NSCLC with subsolid, solid and GGO nodules. (*p < 0.05.**p < 0.01)

Fig. 2

ROC curve analyses of the use of CTC, CEA and imaging examinations to differentiate patients with NSCLC from those with benign lung disease. (A) Combining CTC with nodule density, nodule size, nodule location, and CEA significantly improved the sensitivity and specificity of the diagnosis. Nodular density, CEA and CTC are independent prognostic factors. (B) The relationship between CTCs and CEA values in upper lobe, subsolid and ≥ 8-mm nodules, using the CTC threshold of 12 units/6 ml and the CEA threshold of 1.78 ng/ml

Fig. 3

CTC counts in patients with lung cancer. (A) CTC counts in patients with nodules in the upper lobe of the lung and other sites. (B) CTC counts in patients with ADC with ACIS, MIA, and ADI. (*p < 0.05.**p < 0.01)