Human Plasma Levels of VEGF-A, VEGF-C, VEGF-D, their Soluble Receptor - VEGFR-2 and Applicability of these Parameters as Tumor Markers in the Diagnostics of Breast Cancer

Abstract

VEGF family members are important factors in promoting angio- and lymphangiogenesis. The aim of this study was to investigate concentrations, diagnostic utility and power of VEGF-A, VEGF-C, VEGF-D and VEGFR-2 in comparison to CA15–3 in breast cancer (BC) patients. The study included 120 BC patients and 60 control patients (28 with benign breast tumors and 32 healthy women). Plasma levels of tested parameters were determined by ELISA, CA15–3 by CMIA. Concentrations of all parameters showed statistical significance when compared BC patients to controls. VEGF-D showed the highest SE (82.50%) in total BC group. Highest SP and PPV in total BC group showed VEGF-A(76.67%;84.78%,respectively), but lower than CA15–3. Highest NPV showed VEGF-C(52.33%), but it was lower than CA15–3. VEGF-C was also the best parameter which had statistically significant AUC in total cancer group (0.7672), but also stages I(0.7684) and II(0.7772). In the total group of BC almost all tested parameters showed statistically significant AUC, but a maximum range was obtained for the combination of VEGF-C + CA15–3(0.8476). The combined analysis of tested parameters and CA15–3 resulted in increase in SE and AUC values, which provides hope for developing a new panel of biomarkers that may be used in the diagnosis of BC in the future.

Plasma Levels and Diagnostic Utility of VEGF in a Three-Year Follow-Up of Patients with Breast Cancer

“…The comparative marker (CA 15-3) showed significantly higher concentrations only in relation to the group of healthy women. Differences between our results and those that were presented in other research papers may be explained by a different composition and selection of study and control groups, as well as a different number of participants [14,16,28].…”

“…The statistical analysis of the obtained test results revealed that the preoperative plasma concentrations of VEGF and the comparative marker CA 15-3 in patients with BC were significantly higher than the concentrations in the control group of healthy women. Similar results have been obtained in our earlier studies [14][15][16]28] and in the studies by other authors [17,29]. A study by Quaranta et al [30] failed to demonstrate a statistically higher VEGF concentration in comparison to healthy subjects, although only 20 women constituted the control group.…”

“…VEGF exerts a specific effect on endothelial cells not only by stimulating cell growth, but also by impacting their migration and vascular permeability [12,13]. Moreover, our own studies [14][15][16] and those of other researchers [17][18][19] have shown an increased expression of VEGF in BC, suggesting its possible prognostic utility. Therefore, new diagnostic methods and markers that are capable of detecting neoplastic lesions as early as possible are still being sought.…”

A randomized single-blinded, parallel-arm group feasibility trial evaluating role of pectoral nerve block on serum vascular endothelial growth factor levels in patients undergoing unilateral modified radical mastectomy

“…VEGF levels in patients with breast cancer depend upon different stages of cancer, tumor bulk, local invasion, on cycles of neoadjuvant chemo-radiotherapy received, estrogen receptor status and menopausal state. 27 Baseline serum VEGF levels varied between two groups in our study, though our small study group was homogenous about hormone receptor-positive status, tumor grade and stage (II and III), surgery performed and neoadjuvant chemotherapy received. One of the common causes of increased levels of VEGF measured in serum samples is its release from platelets at the time of venipuncture.…”

VEGFR-Mediated Cytotoxic Activity of Pulicaria undulata Isolated Metabolites: A Biological Evaluation and In Silico Study

“…The plasma level of VEGF-B is a sensitive marker in breast cancer [ 34 ]. VEGF signaling involves the binding of the VEGF ligand to receptor tyrosine kinases VEGFR-1, VEGFR-2 and VEGFR-3, resulting in angiogenesis, vasculogenesis and lymphangiogenesis [ 35 ].…”