Monika Zajkowska

Plasma levels and diagnostic utility of VEGF, MMP-9, and TIMP-1 in the diagnosis of patients with breast cancer.

Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 may play a role in the pathogenesis of cancer disease. We investigated their levels and utility in comparison to cancer antigen (CA) 15-3 in patients with breast cancer (BC) and in relation to the control groups. The study included 100 women with BC, 50 patients with benign breast tumor, and 50 healthy women. The plasma levels of the tested parameters were determined using enzyme-linked immunosorbent assay, while CA 15-3 with chemiluminescent microparticle immunoassay. The results demonstrated significant differences in the concentration of the tested parameters and CA 15-3 between groups of patients with BC and healthy patients or patients with benign breast tumor. The plasma levels of VEGF and tissue inhibitor of metalloproteinase-1 were significantly higher in advanced tumor stages. The tested parameters were comparable to CA 15-3 values of the diagnostic sensitivity, specificity, the predictive values of positive and negative test results, and the area under the receiver-operating characteristic curve. The combined use of the tested parameters with CA 15-3 resulted in the increase in sensitivity, negative predictive value, and area under the receiver-operating characteristic curve, especially in the combination of VEGF with tumor marker (84%, 73%, 0.888, respectively). These findings suggest the usefulness of the tested parameters in the diagnosis of BC. VEGF, especially in combination with CA 15-3, showed the highest usefulness in the diagnosis of early BC.

Diagnostic Power of Vascular Endothelial Growth Factor and Macrophage Colony-Stimulating Factor in Breast Cancer Patients Based on ROC Analysis

Breast cancer (BC) is the most common malignancy in women. Vascular endothelial growth factor (VEGF) has been described as an important regulator of angiogenesis which plays a vital role in the progression of tumor. Macrophage colony-stimulating factor (M-CSF) is a cytokine whose functions include regulation of hematopoietic lineages cells growth, proliferation, and differentiation. We investigated the diagnostic significance of these parameters in comparison to CA15-3 in BC patients and in relation to the control group (benign breast tumor and healthy women). Plasma levels of the tested parameters were determined by ELISA and CA15-3 was determined by CMIA. VEGF was shown to be comparable to CA15-3 values of sensitivity in BC group and, what is more important, higher values in early stages of BC. VEGF was also the only parameter which has statistically significant AUC in all stages of cancer. M-CSF has been shown to be comparable to CA15-3 and VEGF, specificity, and AUC values only in stages III and IV of BC. These results indicate the usefulness and high diagnostic power of VEGF in the detection of BC. Also, it occurred to be the best candidate for cancer diagnostics in stages I and II of BC and in the differentiation between BC and benign cases.

Plasma levels and diagnostic utility of VEGF, MMP-2 and TIMP-2 in the diagnostics of breast cancer patients

Abstract Objective: We investigated plasma levels and diagnostic utility of vascular endothelial growth factor VEGF, matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-2 (TIMP-2) in comparison to cancer antigen 15-3 (CA 15-3). Methods: Plasma levels of tested parameters were determined using enzyme-linked immunosorbent assay (ELISA) while CA 15-3 with chemiluminescent microparticle immunoassay (CMIA). Results: The plasma levels of VEGF, TIMP-2 showed significantly higher than CA 15-3 values of the diagnostic sensitivity, the predictive values of positive and negative test results (PPV, NPV) and the area under the receiver-operating characteristics (ROC) curve (AUC) in early stages of breast cancer (BC). The combined use of the tested parameters with CA 15-3 resulted in the increase in sensitivity, NPV and AUC, especially in the combination with VEGF (83%; 72%; 0.888) and TIMP-2 (83%; 72%; 0.894). The highest values were obtained for combination of all three parameters (93%; 85%; 0.923). Conclusions: These findings suggest the usefulness of the tested parameters in the diagnosis of BC, especially VEGF and TIMP-2 with CA 15-3 in early stages of BC, which could be a new diagnostic panel.

Plasma levels and diagnostic utility of macrophage-colony stimulating factor, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 as tumor markers in cervical cancer patients

Macrophage-colony stimulating factor, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 may play an important role in malignant processes. The aim of this study was to investigate the diagnostic power of those parameters (serological biomarkers) in comparison to cancer antigen 125 and squamous cell carcinoma antigen in cervical cancer patients and in relation to the control groups. The study included 100 cervical cancer patients, 50 patients with cervical ectropion and 50 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, cancer antigen 125, and squamous cell carcinoma antigen by chemiluminescent microparticle immunoassay. Plasma levels of all parameters in the total cancer group showed statistical significance (in all cases p < 0.05). In stage I of cancer only medial supraclavicular fossa and tissue inhibitor of metalloproteinase-1, in stage II all the tested parameters and cancer antigen 125, and in stage III + IV macrophage-colony stimulating factor, matrix metalloproteinase-9, and cancer antigen 125 showed statistical significance when compared to the healthy volunteers group. Macrophage-colony stimulating factor showed the highest value of sensitivity from all tested parameters (I: 56.25%, II: 72.73%, III + IV: 77.14% and 69% in total cervical cancer group). The highest specificity was obtained by matrix metalloproteinase-9 (94%). Positive predictive values were highest also for matrix metalloproteinase-9 (I: 82.35%, II: 84.21%, III + IV: 88% and 94.55% in total cervical cancer group), negative predictive values for macrophage-colony stimulating factor (I: 75.44%, II: 82.69%, III + IV: 87.5% and 58.11% in total cervical cancer group) and tumor markers. In the total cervical cancer group, all tested parameters showed statistically significant areas under receiver operating characteristic curve, but maximum range was obtained for the combination macrophage-colony stimulating factor + squamous cell carcinoma antigen (0.8723). The combined analysis of tested parameters and tumor markers resulted in an increase in sensitivity and areas under receiver operating characteristic curve values, which provides hope for developing new panel of biomarkers that may be used in the diagnosis of cervical cancer in the future.

Human Plasma Levels of Vascular Endothelial Growth Factor, Matrix Metalloproteinase 9, and Tissue Inhibitor of Matrix Metalloproteinase 1 and Their Applicability as Tumor Markers in Diagnoses of Cervical Cancer Based on ROC Analysis

Cervical cancer (CC) remains a major diagnostic problem. The introduction of human papillomavirus vaccination significantly reduced the number of new cases; however, the search for new methods that would earlier indicate the development of cancerous changes is vital. The aim of this study was to investigate the diagnostic power of those parameters in comparison to Cancer Antigen 125 (CA 125) and Squamous Cell Carcinoma Antigen (SCC-Ag) in patients with CC and in relation to the control group. The study included 100 patients with CC and 50 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA 125, and SCC-Ag by chemiluminescent microparticle immunoassay. Plasma levels of all parameters in the total cancer group showed statistical significance (in all cases P < .05). In stage I cancer, only vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinase 1; in stage II, all the tested parameters and CA 125; and in stage III + IV, VEGF, matrix metalloproteinase 9 (MMP-9), and CA 125 showed statistical significance when compared to the healthy volunteers group. Vascular endothelial growth factor showed the highest value of sensitivity from all tested parameters (I: 75%, II: 76%, III + IV: 94%, and 82% in total CC group). The highest specificity was obtained by MMP-9 (94%). In the total CC, stage I, and stage II groups, all tested parameters showed statistically significant area under the receiver operating characteristics curve (AUC), but maximum range was obtained for the combination VEGF + SCC-Ag (I: 0.9146, II: 0.8941, III + IV: 0.9139, total CC group: 0.9347). The combined analysis of tested parameters and tumor markers resulted in an increase in sensitivity and AUC values, which provides hope for developing new panel of biomarkers that may be used in the diagnosis of CC in the future.

Plasma levels of MMP-7 and TIMP-1 in laboratory diagnostics and differentiation of selected histological types of epithelial ovarian cancers

BackgroundMMP-7 and TIMP-1 may play a role in the pathogenesis of cancer disease. In this study we investigated plasma levels of selected metalloproteinase and its tissue inhibitor in comparison to plasma levels of the commonly accepted tumor markers (CA 125 and HE4) in selected histological types of epithelial ovarian cancer patients as compared to control groups: patients with a benign ovarian tumor and healthy subjects. Plasma levels of MMP-7 and TIMP-1 were determined using ELISA, CA 125 and HE4 – by CMIA methods.ResultsPlasma levels of all biomarkers studied were significantly higher in ovarian cancer patients as compared to both control groups. MMP-7 demonstrated comparable to HE4 or CA125 values of diagnostic sensitivity (SE: 61%; 68%; 58%, respectively), specificity (SP: 95%; 95%; 98%, respectively), positive (PPV: 93%; 96%; 98%, respectively) and negative predictive values (NPV: 61%; 66%; 60%, respectively) in the groups tested. The combined use of the aforementioned biomarkers resulted in a further increase in diagnostic criteria and AUC, especially in the early stages of the disease.ConclusionsThese findings suggest the usefulness of combining MMP-7 with CA 125 and HE4 in the diagnosis of epithelial ovarian cancer as a new tumor marker panel.

Plasma Chemokine CCL2 and Its Receptor CCR2 Concentrations as Diagnostic Biomarkers for Breast Cancer Patients

The aim of this study was to investigate plasma levels and applicability of CCL2, CCR2, and tumor marker CA 15-3 in breast cancer (BC) patients and in relation to the control groups: patients with benign breast tumor and healthy subjects. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay (ELISA) and CA 15-3 by Chemiluminescent Microparticle Immunoassay (CMIA). The median levels of CCL2 in entire group of BC were significantly higher compared to the control groups, similarly as median levels of CA 15-3. CCR2 is a negative marker whose levels were significantly lower in BC group compared to healthy women. The concentration of CCL2 in BC increases with advancing tumor stage, while a median level of CCR2 decreases with advancing stage. CCL2 showed the highest value of sensitivity (SE) (64.95%) in entire BC group and also in early stages of disease. The highest specificity (SP) was obtained by CA 15-3 (85.71%). The area under the ROC curve (AUC) of CCR2 (0.7304) was the largest of all the tested parameters (slightly lower than CA 15-3) in the entire BC group, but a maximum range was obtained for the combination of all tested parameters with CA 15-3 (0.8271). In early stages of BC the highest AUC of all tested parameters was observed in CCL2 or CCR2 (stage I: 0.6604 and 0.6564; respectively; stage II: 0.7768, respectively, for CCR2). The findings of this study suggest that there may be applicability of CCL2, CCR2 in diagnosis of BC patients, particularly in conjunction with CA 15-3.

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.

Narrowband ultraviolet B light treatment changes plasma concentrations of MMP-3, MMP-9 and TIMP-3 in psoriatic patients

Background Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are thought to be associated with the pathogenesis and spread of psoriatic disease. This study was designed to investigate the plasma levels of MMP-3, MMP-9 and TIMP-3 in plaque psoriasis patients prior to and following a course of ultraviolet B narrowband treatment with respect to disease advancement. Methods Plasma samples of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were evaluated. Concentrations of MMP-3, MMP-9 and TIMP-3 were determined using enzyme-linked immunosorbent assay, while Psoriasis Area and Severity Index was used to define disease advancement. Results Plasma levels of MMP-3, MMP-9 and TIMP-3 were significantly elevated in psoriasis patients compared to healthy individuals. A course of ultraviolet B narrowband treatment resulted in a significant decline in the studied metalloproteinases. Furthermore, the concentration of selected tissue inhibitors was negatively correlated with baseline Psoriasis Area and Severity Index score. Conclusion Our research highlights the meaningful role of MMP-3, MMP-9 and TIMP-3 in psoriasis pathogenesis and clearance of disease symptoms. Furthermore, plasma levels of the analyzed metalloproteinases seem to be a valuable psoriasis biomarker.

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.