CCR7-Positive Circulating Tumor Cells as a Biomarker for Predicting Lung Cancer Risk

Objective This study aims to investigate the clinical significance of CCR7-expressing circulating tumor cells (CTCs) in lung cancer,with a particular focus on their association with epithelial-mesenchymal transition (EMT) and disease progression. Methods Using CanPatrol™ nanomembrane filtration and RNA in situ hybridization, we analyzed CTCs from 213 lung cancer patients. These CTCs were classified into epithelial, mesenchymal, or hybrid phenotypes, and CCR7 expression was assessed. Clinical correlations were evaluated using Spearman and Pearson correlation analyses, as well as Cox regression. Results The baseline circulating tumor cell (CTC) positivity rate was 81.2%, with mesenchymal CTCs accounting for 44.1% of the positive cases. The overall CCR7 positivity in CTCs was 58.4%, which was significantly higher in adenocarcinoma (58.4%) compared to squamous cell carcinoma (45.9%, P = 0.038). Furthermore, CCR7 expression exhibited a strong correlation with disease progression (r = 0.264, P < 0.001) and served as an independent predictor of poor prognosis (HR = 2.6, 95% CI: 1.8–3.7, P < 0.001). Although mesenchymal CTCs displayed a higher CCR7 positivity rate (27.9%) than their epithelial (27.2%) or hybrid (31.4%) counterparts, this difference was not statistically significant (P > 0.05). Conclusions This study investigates the correlation between CCR7 + CTCs and the progression of lung cancer. The findings demonstrate that CCR7 + CTCs are significantly linked to aggressive disease progression, particularly within adenocarcinoma subtypes. Data reveal a higher prevalence of CCR7 positivity among adenocarcinoma patients, suggesting a connection between its expression and disease advancement. CCR7 appears to activate signaling pathways that promote tumor migration, invasion, and proliferation, potentially through the process of epithelial-mesenchymal transition (EMT). Consequently, CCR7 + CTCs may serve as a valuable biomarker for lung cancer, particularly in cases of adenocarcinoma. The detection of CCR7 in CTCs could improve clinical assessments and facilitate early intervention. However, this study acknowledges certain limitations, including a lack of comprehensive consideration of drug effects on CTCs and a relatively small sample size, highlighting the necessity for further investigation.