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 epithelial-mesenchymal transition (EMT) process, thereby mediating tumor metastasis. However, the dynamic changes and clinical value of mesenchymal CTCs ((CTCs)-C-M) in colorectal cancer (CRC) patients remain inconclusive. The aim of the present study was to explore the prognostic value of dynamic changes of (CTCs)-C-M in CRC patients using our previously developed CTCBIOPSY (R) device with an immunocytochemistry assay. The results revealed that 74 out of 175 patients were pre-(CTCs)-C-M-positive and 41 out of 127 patients were post-(CTCs)-C-M-positive. Dynamical monitoring revealed that the status of (CTCs)-C-M 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, Kaplan-Meier survival analyses revealed that the median recurrence-free survival (RFS) and overall survival (OS) were significantly different between four groups (pre-(CTC-)-C-Mpost-(CTC-)-C-M; pre-(CTC-)-C-M -> post-(CTC+)-C-M; pre-(CTC+)-C-M -> post-(CTC-)-C-M; pre-(CTC+)-C-M -> post-(CTC+)-C-M), and patients with pre-(CTCs+)-C-M -> post-(CTCs+)-C-M 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 (CTCs)-C-M before and after anticancer therapy was an independent risk factor affecting the RFS (HR: 1.302, 95%CI: 1.033-1.639, P=0.025) and OS (HR: 1.366, 95%CI: 1.070-1.742, P=0.012) of CRC patients. Collectively, these findings provided the evidence that the dynamic change of (CTCs)-C-M during anticancer therapy can be a useful prognostic tool in CRC, indicating the important value of molecular profiling of CTCs-EMT traits in cancer management.