Expression of vascular endothelial growth factor in circulating tumor cells for prediction of colorectal cancer

Objectives: Previous studies used enumerated circulating tumor cells (CTCs) to predict prognosis and therapeutic effect in several types of cancers. However, increasing evidence showed that only enumerated CTCs were not enough to reflect the heterogeneity of tumor. Therefore, we classified different metastasis-potential of CTCs from colorectal cancer patients, in order to improve accuracy of the prognosis by CTCs. Methods: Blood samples were collected from 45 primary colorectal cancer patients. CTCs were enriched by blood filtration, and the RNA in situ hybridization method was used to identify and discriminate subgroups of CTCs. Afterwards, vascular endothelial growth factor (VEGF) expression in individual CTCs was measured. Results: Three CTCs subgroups (epithelial/biophenotypic/mesenchymal CTCs) were identified using epithelial-mesenchymal transition (EMT) markers. In our research, mesenchymal CTCs significantly increased along with tumor progression, including developing distant metastasis and vascular invasion. Furthermore, VEGF expression rate in mesenchymal CTCs was significantly higher than that of epithelial CTCs, which suggested that VEGF may be correlated with tumor malignancy. This hypothesis was further verified by VEGF expression in mesenchymal CTCs strictly related to tumor aggressiveness factors. Finally, we revealed that mesenchymal CTCs and VEGF expression may predict high risk subgroups in stage II colorectal cancer. Conclusions: Our research proved that CTCs could serve as feasible surrogate samples to detect gene expression as a predictive biomarker for tumor evaluation.