Circulating tumor cells are associated with lung cancer subtypes: a large-scale retrospective study.

Background: Circulating tumor cells (CTCs) provide a unique resource to decipher cell molecular properties of lung cancer. However, the clinicopathologic and radiological features associated with CTCs in different lung cancer subtypes remain poorly characterized. The aim of this study was to explore the clinicopathological and radiological features of CTCs in different lung cancer subtypes. Methods: The CTC data were obtained using the CellSearch Circulating Tumor Cell Kit. CTCs were detected in 5,128 surgical patients with lung adenocarcinoma (LUAD), 2,226 with lung squamous cell carcinoma (LUSC), 248 with small cell lung cancer (SCLC), 99 with large cell carcinoma, and 70 with metastatic carcinomas. A Pearson correlation analysis was conducted to analyze the patients' clinical information, radiological features, and molecular characteristics, and logistic regression was used to examine the correlations between these factors and CTCs. Results: For LUAD, the presence of tumor lobation, air bronchogram, and the epidermal growth factor receptor (EGFR) mutation were significantly associated with CTC levels. While the multivariable logistic regression analysis indicated that CD68 and P40 expression were independent factors associated with CTCs. For LUSC, tumor size, tumor spiculation, pleural indentation, air bronchogram, the expression levels of CK8/18, GPA33, and leucocyte common antigen (LCA) were significantly associated with CTC levels. The multivariable logistic regression analysis indicated that tumor size, pleural indentation, and air bronchogram were independent factors affecting CTCs. For SCLC, no factors were found to be significantly associated with CTC levels. For large cell carcinoma, tumor lobation and spiculation were significantly associated with CTC levels. For metastatic lung cancers, the presence of the positive lymphoid node was the only factor significantly associated with CTC levels. Conclusions: We conducted a comprehensive analysis of the tumor properties, radiological features, and genomic characteristics that are significantly associated with CTCs in different lung cancer subtypes. This study helps elucidate the formation mechanism and relevant major regulation molecules of CTCs.