The Role of Circulating Tumor Cell as a Promising Biomarker in the Evaluation of Pulmonary Nodules: A Prospective Study.

Abstract

Purpose: Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis.

Materials and methods: Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operator characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic-clinical characteristics were analyzed. LC-WGS-based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted.

Results: A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases.

Conclusion: CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with CT imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.