Clinical and biological significance of circulating tumor cells, circulating tumor DNA, and exosomes as biomarkers in colorectal cancer
Circulating tumor cells (CTCs) with phenotypic hallmarks of epithelial-mesenchymal transition (EMT) reportedly contribute to tumor metastasis in different cancer types. We therefore evaluated the expression of EMT markers in CTCs obtained from a large cohort of Chinese patients with colorectal cancer (CRC) and investigated their clinical relevance. The CanPatrolTM CTC enrichment technique was used to isolate and classify CTCs. CTCs were detected in 1046 of 1203 patients (86.9%), and three phenotypes were identified based on the expression of epithelial and mesenchymal markers: epithelial CTCs, biophenotypic (epithelial/mesenchymal) CTCs, and mesenchymal CTCs. Total CTC numbers positively correlated with both clinical stage and lymph node metastasis and distant metastasis. Furthermore, both biophenotypic and mesenchymal, but not epithelial, CTCs, correlated with the above parameters, suggesting CTCs displaying a mesenchymal phenotype denote more aggressive disease and metastatic potential. This is the first study to demonstrate a significant correlation between CTCs displaying a mesenchymal phenotype and both clinical stage and metastasis in a large cohort of patients with CRC. Our findings suggest that assessment of not only epithelial, but also mesenchymal markers in CTC analyses may offer valuable assistance for tumor staging and metastasis evaluation in patients with CRC.