Soluble VE-cadherin in metastatic breast cancer: an independent prognostic factor for both progression-free survival and overall survival

Abstract

Background:Patients with metastatic breast cancer (MBC) represent a heterogeneous group, with large differences in outcomes from individual patients. VE-cadherin, an endothelial-specific cadherin, was shown to promote tumour proliferation and angiogenesis. Soluble VE-cadherin has been recently associated to breast cancer progression. This study was designed to investigate the prognosis significance of soluble VE-cadherin in hormone-refractory MBC.Methods:Between 2004 and 2007, 150 patients with a fully documented history of hormone-refractory MBC were included in the prospective SEMTOF study. Serum concentrations of VE-cadherin were measured at inclusion for 141 patients and 6 weeks after the beginning of chemotherapy, using a sandwich enzyme immunoassay.Results:The presence of high levels of serum VE-cadherin was significantly correlated to a shorter progression-free (PFS) and overall survival (OS). In a multivariate analysis along with clinical and biologic prognostic parameters, high serum VE-cadherin level was an independent adverse prognostic variable for PFS (median PFS 9.7 (IC95: 8; 11.9) vs 5.8 (IC95: 4.1; 8) months P=0.0008) and OS (median OS 34 (IC95: 26.6; 47.1) vs 14.8 (IC95: 9.3; 21.4) months P=0.0007). Moreover, VE-cadherin decrease during chemotherapy was also associated with good prognosis.Conclusions:Serum VE-cadherin levels correlate to poorer survival in patients with hormone-refractory MBC. As sVE-cadherin reflects tumour angiogenesis, this could have therapeutic implications for antiangiogenic treatment.

Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells

“…VE-Cadherin is a well-known factor for increased vascular permeability in estrogen-positive breast cancer 57 and its expression correlates with poor survival prognosis in human gastric cancer and can therefore be used as a biomarker 58,59 . VE-Cadherin expression has been related to melanoma 60 and breast cancer progression 61 . Nevertheless, the presence of VE-Cadherin in exosomes or the possible effects that these vesicles may have in the tumorigenic potential of breast cancer cells has not been previously determined.…”

Chemotherapy administration to breast cancer patients affects extracellular vesicles thrombogenicity and function

“…Previous studies found that interaction of BC cells with endothelial cells leads to phosphorylation of VE-cadherin and disruption of endothelial adherent junction [ 24 ]. High levels of serum VE-cadherin were significantly correlated to a shorter progression-free and overall survival [ 25 ]. We can assume that the presence of tumor and tumor-related EVs in the neo-adjuvant patients or a short period after surgery in the adjuvant patients induced tissue and vascular damage prior to chemotherapy.…”

Cadherin 5 Ιs a Significant Risk Factor for Hematogenous Recurrence and a Prognostic Factor in Locally Advanced Gastric Cancer

“…In conclusion, high CDH5 immunohistochemical expression was a significant risk factor for hematogenous recurrence and was a predictor of survival in locally advanced GC treated by surgery alone. Serum soluble CDH5 could be measured and was an independent prognostic factor in breast cancer (29); therefore, serum CDH5 should be evaluated in patients with GC in the future. The inhibition of CDH5 may serve as a target for the prevention of tumor angiogenesis and hematogenous metastasis in GC.…”