Value of Circulating Tumor Cells in the Diagnosis and Treatment of Solitary Pulmonary Nodules

Background: Lung cancer has become the most common malignant tumor worldwide, with the highest rates of morbidity and mortality. The detection of circulating tumor cells (CTCs) can be simple, rapid, and minimally invasive, thus endowing them with a high value in the diagnosis of malignant tumors. We aimed to explore the correlation between CTCs in peripheral blood and benign or malignant solitary pulmonary nodules (SPNs).

Methods: A total of 223 patients with SPNs from January 2018 to May 2020 were recruited. During the same period, 20 healthy volunteers were recruited as controls. Venous blood samples were collected from participants for detecting CTCs using a folate receptor (FR)-positive cell detection kit, as well as tumor biomarkers.

Results: A significant difference in the level of CTCs were observed between the malignant SPNs group, the benign SPNs group, and the control group, which was markedly higher in the malignant SPNs group (10.48±3.49 FU/3 mL) than both the benign SPNs and control groups (6.38±0.53 and 4.45±1.21 FU/3 mL, respectively) (P<0.001). In addition, the level of CTCs was significantly higher in the benign SPNs group than in the control group (P=0.023). In particular, in the malignant SPNs group, patients older than 60 years (11.45±3.92 FU/3 mL) presented a notably higher level of CTCs than other patients (9.55±2.74 FU/3 mL). The patients were then classified according to the pathological subtypes of lung cancer. There was a significant difference in level of CTCs among patients with squamous cell carcinoma (9.10±1.94 FU/3 mL), adenocarcinoma (10.77±3.71 FU/3 mL), and adenosquamous cell carcinoma (11.78±2.61 FU/3 mL). Binary logistic regression analysis suggested that CTCs were an independent risk factor of malignant SPN (OR =3.698, 95% CI: 1.136-11.035, P=0.030). The sensitivity and specificity of CTCs in diagnosing malignant SPNs was significantly higher than tumor biomarkers (single or combined) [sensitivity =89.1%; specificity =92.3%; area under curve (AUC) (95% CI) =0.907 (0.861-0.942)].

Conclusions: Peripheral blood CTCs can be used in the diagnosis of malignant SPNs and are recommended for clinical application.