Dynamic evaluation of mesenchymal circulating tumor cells in patients with colorectal cancer: Clinical associations and prognostic value.

Circulating tumor cells (CTCs), as the precursor of metastases, gain mesenchymal traits through the epithelial­mesenchymal transition (EMT) process, thereby mediating tumor metastasis. However, the dynamic changes and clinical value of mesenchymal CTCs (MCTCs) in colorectal cancer (CRC) patients remain inconclusive. The aim of the present study was to explore the prognostic value of dynamic changes of MCTCs in CRC patients using our previously developed CTCBIOPSY® device with an immunocytochemistry assay. The results revealed that 74 out of 175 patients were pre­MCTCs­positive and 41 out of 127 patients were post­MCTCs­positive. Dynamical monitoring revealed that the status of MCTCs remained dynamically changed under the pressure of anticancer therapy, and these dynamic changes were significantly associated with lymphovascular invasion (P<0.001) and TNM stage (P=0.033). Moreover, Kaplan­Meier survival analyses revealed that the median recurrence­free survival (RFS) and overall survival (OS) were significantly different between four groups (pre­MCTC­â†’post­MCTC­; pre­MCTC­â†’post­MCTC+; pre­MCTC+→post­MCTC­; pre­MCTC+→post­MCTC+), and patients with pre­MCTCs+→post­MCTCs+ had a significant shorter RFS (P=0.001) and OS (P<0.001) than the others. Univariate and multivariate Cox regression analyses demonstrated that persistent positivity of MCTCs before and after anticancer therapy was an independent risk factor affecting the RFS (HR: 1.302, 95%CI: 1.033­1.639, P=0.025) and OS (HR: 1.366, 95%CI: 1.070­1.742, P=0.012) of CRC patients. Collectively, these findings provided the evidence that the dynamic change of MCTCs during anticancer therapy can be a useful prognostic tool in CRC, indicating the important value of molecular profiling of CTCs­EMT traits in cancer management.