Linking EMT Status of Circulating Tumor Cells to Clinical Outcomes in Lung Cancer

Yun Huangfu,1,* Jianxin Guo,1,* Yang Zhao,1,* Xuexia Cao,1 Lei Han2 1Henan Medical College, Zhengzhou, Henan Province, People’s Republic of China; 2Henan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Han, Henan Eye Hospital, Henan Provincial People’s Hospital, No. 7 Weiwu Road, Zhengzhou, Henan Province, People’s Republic of China, Tel +86-15937121171, Email hanlei2006ray@163.comBackground: Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, with its prognosis influenced by complex biological factors.Objective: This study delves into the clinical relevance of circulating tumor cells (CTCs) and their Epithelial-Mesenchymal Transition (EMT) status in LC patients.Methods: We enrolled 30 newly diagnosed LC patients and utilized the CanPatrol technique for the separation and categorization of CTCs from peripheral blood samples. Immunofluorescent staining identified epithelial (CK8/18/19, EpCAM), mesenchymal (Vimentin, Twist), and leukocyte (CD45) markers in these cells. Fluorescence microscopy analyzed the slides, and RECIST 1.1 criteria assessed treatment response. Spearman’s method was used to correlate CTCs’ EMT states with their count and clinical characteristics.Results: Our findings reveal three distinct CTC groups: epithelial (E-CTCs), hybrid epithelial/mesenchymal (E/M-CTCs), and mesenchymal (M-CTCs). Significant statistical differences were observed in stages III–IV vs I–II, tumor sizes T3-T4 vs T1-T2, and in the presence or absence of distant metastasis and lymph node involvement. Notably, the count of E/M-CTCs was positively correlated with TNM staging, tumor size, lymph node, and distant metastasis. Changes in M-CTC count pre- and post-treatment closely mirrored disease progression and control, showing considerable consistency with RECIST criteria.Conclusion: In conclusion, the EMT status of CTCs, especially E/M-CTCs, holds predictive value for LC staging, tumor size, and metastasis. Dynamic monitoring of M-CTCs can accurately reflect disease progression.Keywords: lung cancer, circulating tumor cells, epithelial-mesenchymal transition, canpatrol technique, CTC classification