Diagnostic power of VEGF, MMP-9 and TIMP-1 in patients with breast cancer. A multivariate statistical analysis with ROC curve.

PURPOSE: Vascular endothelial growth factor is an important factor in promoting angiogenesis in malignant processes, matrix metalloproteinase-9 in the degradation of extracellular matrix, which enhances metastasis, and tissue inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to investigate the diagnostic power of these parameters in comparison to CA15-3 in breast cancer patients and in relation to the control group. MATERIALS/METHODS: The study included 120 breast cancer patients, 60 patients with benign breast tumors and 60 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle immuno assay. RESULTS: Tissue inhibitor of metalloproteinase-1 showed the highest value of sensitivity in breast cancer group (86.25%) and, more importantly, highest value in breast cancer stage I (85%). Vascular endothelial growth factor also showed high sensitivity (stage I and II-75%, III-85%, IV-70% and 76.25% in total breast cancer group) and the highest specificity (85%) from all tested parameters. It was also the only parameter which had statistically significant area under curve in all stages. In the total breast cancer group all tested parameters showed statistically significant area under curve, but the maximum range was obtained for combination: 'vascular endothelial growth factor + CA15-3'. Vascular endothelial growth factor seems to be the best candidate for diagnosing breast cancer stage I and for differentiating between breast cancer and non-carcinoma cases. CONCLUSIONS: The combined analysis of tested parameters and CA15-3 resulted in an increase in sensitivity and area under curve values, which provides hope for developing new panel of biomarkers that may be used in diagnosing breast cancer in the future.

ROC analysis of selected matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in psoriatic patients.

INTRODUCTION: Psoriasis is a common, chronic inflammatory disease characterised by typical scaly skin lesions. The role of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis and development of this condition have been repeatedly emphasised in available literature. AIM: ROC analysis of selected MMPs (MMP-2, MMP-3, MMP-9, MMP-12, TIMP-2) and TIMPs (TIMP-2, TIMP-3) in psoriasis patients. The area under the ROC curve (AUC) indicates the clinical usefulness of a biomarker and its diagnostic power. MATERIAL AND METHODS: Plasma samples of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were evaluated. Concentrations of MMPs and TIMPs were determined using the enzyme-linked immunosorbent assay (ELISA) while Psoriasis Area and Severity Index (PASI) was used to define disease advancement. RESULTS: In the total psoriasis patients group, the largest area under the ROC curve was obtained for TIMP-3. After the division of the total group based on disease severity, the highest AUC of all tested parameters was observed for patients with mild disease severity and subgroup Ia for TIMP-3, for subgroup Ib for MMP-12, and for individuals with moderate disease severity for MMP-2. The combined analysis of all tested parameters showed an increase in AUC values in the total group examined as well as in all groups of disease severity. CONCLUSIONS: These results indicate the usefulness and high diagnostic power of TIMP-3 in early detection of psoriasis. Additionally, the combination of all tested parameters appeared to be a valuable biomarker panel for the analysed disease.

Influence of narrowband ultraviolet-B phototherapy on plasma concentration of matrix metalloproteinase-12 in psoriatic patients.

INTRODUCTION: Matrix metalloproteinase-12 (MMP-12) may play an important role in the pathogenesis and spread of psoriatic disease. AIM: To investigate plasma levels of the selected enzyme in plaque psoriasis patients before and after the course of narrowband UVB (NBUVB) therapy with respect to disease advancement. MATERIAL AND METHODS: The cohort included 49 patients suffering from plaque psoriasis, divided into groups according to severity of the disease. The control group consisted of 40 healthy volunteers. Plasma levels of MMP-12 were determined using immunoenzyme assay (ELISA), while the Psoriasis Area and Severity Index (PASI) was used to define disease advancement. RESULTS: The results have shown a significantly decreased plasma level of MMP-12 in the total psoriasis patient group compared to healthy individuals, declining with the increase in disease advancement. The NBUVB therapy caused a decrease in the concentration of the analyzed enzyme, but this change was not statistically significant in the total group of psoriatic patients, while a significant change was detected in patients with a mild advancement of the disease. CONCLUSIONS: Decreased synthesis of MMP-12 may lead to the stimulation of the epidermal angiogenesis process, which results in the appearance and spread of psoriatic scales. Based on the obtained results, macrophage metalloelastase seems to be a negatively reacting plasma biomarker of the studied disease.

Plasma Levels and Diagnostic Utility of M-CSF, MMP-2 and its Inhibitor TIMP-2 in the Diagnostics of Breast Cancer Patients.

BACKGROUND: M-CSF, MMP-2 and its inhibitor TIMP-2 may play a role in the pathogenesis and proliferation of breast cancer (BC). In this paper, plasma levels and the diagnostic utility of these parameters were investigated in comparison to CA 15-3 in patients with BC and in relation to the control groups: patients with benign breast tumor and healthy subjects. METHODS: Plasma levels of the tested parameters were determined using immunoenzyme assay (ELISA) and CA 15-3 with a chemiluminescence method (CMIA). RESULTS: Our results demonstrated significant differences in the concentration of the tested parameters and CA 15-3 between BC patients and healthy subjects or benign breast tumor patients. Only the plasma levels of TIMP-2 were significantly higher at all tumor stages (I - IV) when compared to healthy controls. M-CSF and TIMP-2 values were comparable to CA 15-3 values for the diagnostic sensitivity, specificity, the predictive values of positive and negative test results (PPV, NPV) and the area under the ROC curve (AUC) in the total BC group. The combined use of the tested parameters with CA 15-3 resulted in the increase in sensitivity, NPV, and AUC, especially in the combination of M-CSF with comparative tumor marker (78%;65%;0.866, respectively) and TIMP-2 with comparative tumor marker (84%;71%;0.895, respectively). CONCLUSIONS: These findings suggest the usefulness of the tested parameters in the diagnosis of BC. However, the highest usefulness in the diagnostics of early BC (stage I and II) was found in case of TIMP-2 (particularly for differential diagnosis between BC and benign breast tumor) and M-CSF, especially with CA 15-3, which could be a new diagnostic panel.