CD26-positive/CD326-negative circulating cancer cells as prognostic markers for colorectal cancer recurrence

The present study evaluated the presence and clinical relevance of a cluster of differentiation (CD)26⁺/CD326^- subset of circulating tumor cells (CTCs) in pre- and post-operative blood samples of colorectal cancer patients, who had undergone curative or palliative intervention, in order to find a novel prognostic factor for patient management and follow-up. In total, 80 colorectal cancer patients, along with 25 healthy volunteers were included. The easily transferable methodology of flow cytometry, along with multiparametric antibody staining were used to selectively evaluate CD26⁺/CD326^- CTCs in the peripheral blood samples of colorectal cancer patients. The multiparametric selection allowed any enrichment methods to be avoided thus rendering the whole procedure suitable for clinical routine. The presence of CD26⁺/CD326^- cells was higher in advanced Dukes' stages and was significantly associated with poor survival and high recurrence rates. Relapsing and non-surviving patients showed the highest number of CD26⁺/CD326^- CTCs. High pre-operative levels of CD26⁺/CD326^- CTCs correctly predicted tumor relapse in 44.4% of the cases, while 69% of post-operative CD26⁺/CD326^- CTC-positive patients experienced cancer recurrence, with a test accuracy of 88.8%. By contrast, post-operative CD26⁺/CD326^- CTC-negative patients showed an increase in the three-year progression-free survival rate of 86%, along with a reduced risk of tumor relapse of >90%. In conclusion, CD26⁺/CD326^- CTCs are an independent prognostic factor for tumor recurrence rate in multivariate analysis, suggesting that their evaluation could be an additional factor for colorectal cancer recurrence risk evaluation in patient management.