Low Phosphatidylserine+ Cells Within the CD34+/CD45dim/CD117(c-Kit)+ Subpopulation Associate with Poor Outcomes in Metastatic Colorectal Cancer

Colorectal cancer is among the most prevalent causes of tumour-related deaths worldwide. Antiangiogenic therapy represents a cornerstone for metastatic CRC treatment and biomarkers are advocated for the optimization of this therapeutic strategy. In this observational prospective study, we applied an optimized flow cytometry (FC) protocol to explore the prognostic and predictive potential of blood circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEPC) and related subsets in a cohort of patients with metastatic colorectal cancer (n=40). Computational FC analysis revealed a differential enrichment of blood cell clusters with a CD34+/CD45dim /CD117(c-kit)+ phenotype between responders and non-responders both to antiangiogenic and non antiangiogenic treatments. Intriguingly, our results show that a high percentage of annexin V negative cells in a putative circulating progenitor population with a CD34+/CD45dim/CD117+ phenotype was correlated with reduced response to systemic anticancer treatments (p 0.005) and worse overall survival (0.03). In addition, we observed increased blood concentrations of CD34+/CD45dim/CD117+/Annexin V- cells in patients with higher number of metastatic sites (p 0.03). Overall, these findings hold promise for the identification of novel blood based biomarkers for improved personalized treatment approaches in patients affected by metastatic colorectal cancer.