The combination of folate receptor-positive circulating tumor cells and serum tumor markers suggests a histological diagnosis of lung cancer

BACKGROUND: Folate-receptor alpha (FRα) is overexpressed in lung carcinoma. The FR-positive circulating tumor cell (FR+ CTC) has been established to be a non-invasive biomarker for lung cancer diagnosis. In this study, we sought to examine the value of FR+ CTC in the histological diagnosis of suspicious space-occupying pulmonary lesions. METHODS: A total of 538 patients with suspicious space-occupying pulmonary lesions were enrolled in this study. FR+ CTCs were detected before treatment initiation using negative enrichment and ligand-targeted polymerase chain reaction assays. The enrolled patients concurrently received serum biomarker tests. RESULTS: A total of 282 lung cancer patients [163 with adenocarcinoma (ADC), 71 with squamous cell carcinoma (SCC), and 48 with small cell lung cancer (SCLC)], and 256 patients with benign disease who concurrently received FR+ CTC and serum biomarker tests were randomly assigned to a training set and a validation set. The FR+ CTC levels of patients with lung cancer were significantly higher than those of patients with benign disease (P<0.001). Compared to serum tumor biomarkers alone, the model combining FR+ CTC and serum biomarkers had the highest area under the receiver operating characteristic curve in the diagnosis of NSCLC, ADC, SCC, and SCLC. CONCLUSIONS: Diagnostic models that include both FR+ CTC and serum biomarkers could increase the efficiency of distinguishing between different histological types of lung cancer and benign space-occupying pulmonary diseases.