Circulating Tumor-Derived Endothelial Cells: An Effective Biomarker for Breast Cancer Screening and Prognosis Prediction

Abstract

Background. Circulating tumor-derived endothelial cell (CTEC) is a new potential tumor biomarker to be associated with cancer development and treatment efficacy. However, few evidences are available for breast cancer. Methods. Eighty-nine breast cancer patients were recruited, and preoperative and postoperative blood samples were collected. Besides, 20 noncancer persons were enrolled as controls. An improved subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) method was adopted to codetect CD31+ aneuploid CTEC and CD31− aneuploid circulating tumor cell (CTC). Then, the clinical significance of CTCs and CTECs on breast cancer screening and prognosis prediction was evaluated and compared. Results. The positive rate of CTCs and CTECs in newly diagnosed breast cancer patients was 68.75% and 71.88%. Among detected aneuploid circulating rare cells, CTEC accounts for a greater proportion than CTC in breast cancer patients. CTEC-positive rate and level were significantly higher in breast cancer patients with lymph node metastasis (LNM) than those without LNM ( P = 0.043 ), while there was no significant difference in CTC. CTEC (area under the curve, AUC = 0.859) had better performance than CTC (AUC = 0.795) to distinguish breast cancer patients from controls by receiver operator characteristic curve analysis. Preoperative CTEC count ≥ 2 was a significant risk factor for reducing PFS of breast cancer patients. Conclusions. CTECs may function as a reliable supplementary biomarker in breast cancer screening and prognosis prediction.

The integrated on-chip isolation and detection of circulating tumour cells

“…, dual EpCAM positive and CD31 positive ) markers. 39,68,95,96 Targeting of malignancy specific markers has also been investigated to address this challenge, including positive selection for prostate specific membrane antigen (PSMA) in prostate cancer and for human epidermal growth factor 2 (HER2) in breast and gastric cancers. 22,97…”

“…79,94 Attempts to mitigate this downregulation have sought to diversify the surface antigens used in antigen-dependant CTC capture by including mesenchymal (e.g., vimentin positive ) and pseudo-endothelial (e.g., dual EpCAM positive and CD31 positive ) markers. 39,68,95,96 Targeting of malignancy specific markers has also been investigated to address this challenge, including positive selection for prostate specific membrane antigen (PSMA) in prostate cancer and for human epidermal growth factor 2 (HER2) in breast and gastric cancers. 22,97 The inverse immune-affinity approach, negative enrichment, makes use of antibody-coated solid supports to target cell surface antigens such as CD45 (specific to white blood cells) to deplete healthy blood cells from a sample.…”