scholarly journals Plasma Matrilysins MMP-7 and MMP-26 Concentrations as Diagnostic Biomarkers for Breast Cancer Patients

2020 ◽  
Author(s):  
Barbara Maria Piskór ◽  
Andrzej Przylipiak ◽  
Emilia Dąbrowska ◽  
Iwona Sidorkiewicz ◽  
Marek Niczyporuk ◽  
...  

Abstract Background: Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are the one of the group of MMPs that could represent potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the a diagnostic utility of studied matrilysins in BC patients. Methods: The study group consisted of 120 patients with BC, the control group consisted of 40 patients with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by Enzyme-Linked Immunosorbent Assay, CA 15-3 by Chemiluminescent Microparticle Immunoassay.Results: The plasma levels of MMP-7 were significantly higher in the entire BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were the highest in the III and IV stage of disease. The highest diagnostic sensitivity was observed in the III and IV stage of cancer for set of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters in all studied BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) set of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in III and IV stage. Also individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of disease. Conclusions: Data suggested that MMP-7 can be considered as additional marker improving diagnostic utility of CA 15-3 in early stages of BC patients. Therefore, combined analysis of MMP-7 and MMP-26 with CA 15-3 might be useful in detection of disease progression. Future investigation is needed to evaluate whether matrilysins might be a potential markers improving diagnosis of BC.

2021 ◽  
Vol 10 (7) ◽  
pp. 1436
Author(s):  
Barbara Maria Piskór ◽  
Andrzej Przylipiak ◽  
Emilia Dąbrowska ◽  
Iwona Sidorkiewicz ◽  
Marek Niczyporuk ◽  
...  

Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are members of the MMPs group that show promise as potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the diagnostic utility of studied matrilysins in patients with BC. The study group consisted of 120 patients with BC, and the control group consisted of 40 subjects with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by enzyme-linked immunosorbent assay, and CA 15-3 by chemiluminescent microparticle immunoassay. Plasma levels of MMP-7 were significantly higher in the BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were highest in stages II and IV of the disease. The highest diagnostic sensitivity was observed in stages III and IV BC for the combination of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters combined in the BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) for the combination of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in stages III and IV. Individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of the disease. Study results indicate that MMP-7 could be used as an additional marker that would improve the diagnostic utility of CA 15-3 in early stages of BC. Therefore, the combined assessment of MMP-7 and MMP-26 with CA 15-3 might be useful in determining disease progression. Further studies are needed to evaluate whether matrilysins show promise as potential markers for improving the diagnosis of BC.


Biomarkers ◽  
2016 ◽  
Vol 22 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Sławomir Ławicki ◽  
Monika Zajkowska ◽  
Edyta Katarzyna Głażewska ◽  
Grażyna Ewa Będkowska ◽  
Maciej Szmitkowski

1987 ◽  
Author(s):  
A Sagripant ◽  
A Carpi ◽  
U Baicchi ◽  
A Nicolini ◽  
M Ferdeghint

As the fibrin clot may play a role in the intravascular metastatic spread of breast cancer, we have treated women with advanced breast cancer with oral anticoagulants. After mastectomy, 11 consentient women with postsurgical stage Nl (6 patients), N2 (3 patients) and N3 (2 patients) and without evidence of distantmetastasis have been treated with acenocoumarol (INR 2-4,5) for 4-22 months (mean 12 months). All the patients received adjuvant therapy (radiotherapy, polichemiotherapy and/or tamoxifen) in conformity with theclassic indications. FibrinopeptideA plasmatic level, checked in everyone on stable anticoagulation, was always lower than 2 ng/ml (mean 0,78 ng/ml). No major bleeding occurred, except a copious hematuria caused by overdosage. Until now all the 11 women are alive. Two of them stopped anticoagulant, one because of hemorrhagic cystitis, the other because of awareness of visceral metastases; all the other 9 women arebeing treated now. Three patients(2N2 and 1 N3) have evidence of visceral metastases; no sign of relapsehas been observed by serial instrumental and laboratory examinations inthe other 8 women. A control group of 13 patients (9 N2 and 4 N3)was compared with the group of anticoagulated patients in more advanced stages (2 N2 and 3 N3):The follow-up of the anticoagulatedNl patients is too brief as yet forcomparative evaluation. Our preliminary data seem to indicate an useful role of oral anticoagulants inbreast cancer and oblige us to prolong investigation.


Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 393 ◽  
Author(s):  
Cesar Ramirez-Tortosa ◽  
Ana Sanchez ◽  
Cristina Perez-Ramirez ◽  
Jose Luis Quiles ◽  
María Robles-Almazan ◽  
...  

The etiology of breast cancer can be very different. Most antineoplastic drugs are not selective against tumor cells and also affect normal cells, leading to a wide variety of adverse reactions such as the production of free radicals by altering the redox state of the organisms. Therefore, the objective of this study was to elucidate if hydroxytyrosol (HT) (an antioxidant present in extra virgin olive oil) has a chemomodulatory effect when combined with the chemotherapeutic drugs epirubicin and cyclophosphamide followed by taxanes in breast cancer patients. Changes in plasma levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) throughout the chemotherapy treatment were studied. Both molecules are involved in cell proliferation, apoptosis, neoangiogenesis, and metastasis in breast cancer patients. Women with breast cancer were divided into two groups: a group of patients receiving a dietary supplement of HT and a control group of patients receiving placebo. The results showed that the plasma levels of TIMP-1 in the group of patients receiving HT were significantly lower than those levels found in the control group after the epirubicin-cyclophosphamide chemotherapy.


Author(s):  
Monika Zajkowska ◽  
Emilia Lubowicka ◽  
Paweł Malinowski ◽  
Maciej Szmitkowski ◽  
Sławomir Ławicki

The VEGF family members are important factors in promoting angiogenesis and lymphangiogenesis in malignant processes. The aim of this study was to investigate plasma concentrations of VEGF-A, VEGF-B and their soluble VEGFR-1 receptor and their diagnostic utility and potency as compared to CA 15-3 in breast cancer patients and in relation to the control group. The study included 120 breast cancer patients and 60 control patients. Plasma levels of tested parameters were determined with ELISA and CA 15-3 levels were determined with CMIA. Concentrations of all tested parameters in breast cancer patients showed statistically significant difference when compared to the control groups (benign breast tumor patients and/or healthy women). VEGF-B showed the highest values of sensitivity (Sn) and predictive value of a negative test result (NPV) in total BC group (90% and 66.7%, respectively) and, more importantly, in stages I–II of BC (SE: 86.8%; 92.7%, NPV: 82.8%; 88.9%, respectively). Among all parameters tested, VEGF-A showed the highest specificity (Sf) (76.7%) and predictive value of a positive test result (PPV) (84.8%), yet they were lower than for CA 15-3. VEGF-A was also the best parameter that had statistically significant Area Under Curve (AUC) in stages I (0.678) and II (0.768). In the whole group of BC patients all parameters tested showed statistically significant AUC, but the maximum range was obtained for the combination of VEGF-A and CA 15-3 (0.817). The combined analysis of the studied parameters and CA 15-3 resulted in an increase in sensitivity and AUC values, which provides hope for developing a new panel of biomarkers that may be used in BC diagnosis in the future.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Emilia Lubowicka ◽  
Andrzej Przylipiak ◽  
Monika Zajkowska ◽  
Barbara Maria Piskór ◽  
Paweł Malinowski ◽  
...  

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.


2019 ◽  
Vol 65 (6) ◽  
pp. 825-831
Author(s):  
Lyudmila Belskaya ◽  
Viktor Kosenok

Currently, the urgent task is to search for new biomarkers as a promising tool for early detection and monitoring of breast cancer. The aim of the study was to study the level of cytokines in the saliva of patients with breast cancer. In the case-control study volunteers participated, which were divided into 3 groups: the main (breast cancer, n = 43), the comparison group (fibroadenoma, n = 32) and the control group (conditionally healthy, n = 39). All participants were questioned; biochemical examination of saliva, histological verification of the diagnosis was carried out. Intergroup differences are estimated by a nonparametric criterion. It is shown that in the context of breast cancer, the level of cytokines (IL-2, IL-4, IL-6, IL-10 and IL-18) is increasing, except for IL-8, the content of which decreases compared to the control group. When the disease progresses by the nature of the dynamics, the parameters are divided into two groups: IL-2, IL-4, IL-18 and IL-6, IL-8, IL-10. For the first group of cytokines, there was a decrease in content during the transition from the early stages to the more common ones. For the second group, when passing from stages T1-2N0M0 to T1-2NjM0, the level of cytokines remains practically constant. In the future, the level of cytokines is observed for stage T3_4N0_2M0, and for IL-2, IL-4 and IL-10, the level of cytokines reaches values corresponding to early stages, whereas for IL-6, IL-8 and IL-18 in the same direction, a significant increase in indicators was noted. Additionally, the IL-6/IL-8 ratio was calculated depending on the tumor size, as well as the presence / absence of metastasis. It is shown that this ratio is statistically significantly increased in the advanced stages of the disease. Particularly interesting is the increase in this ratio in saliva at the initial stages of the disease.


Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 2
Author(s):  
Lee D. Gibbs ◽  
Kelsey Mansheim ◽  
Sayantan Maji ◽  
Rajesh Nandy ◽  
Cheryl M. Lewis ◽  
...  

Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.


2020 ◽  
Vol 9 (12) ◽  
pp. 4122
Author(s):  
Barbara Maria Piskór ◽  
Andrzej Przylipiak ◽  
Emilia Dąbrowska ◽  
Iwona Sidorkiewicz ◽  
Marek Niczyporuk ◽  
...  

Background: Stromelysins are potential breast cancer biomarkers. The aim of the study was to evaluate if plasma levels of selected metalloproteinases (MMPs) (stromelysin-1 (MMP-3) and stromelysin-10 (MMP-10)) and cancer antigen 15-3 (CA 15-3) used separately and in combination demonstrated diagnostic usefulness in breast cancer (BC). Methods: The study group consisted of 120 patients with BC, while the control group included 40 patients with benign breast cancer and 40 healthy individuals. Concentrations of MMP-3 and MMP-10 were determined by enzyme-linked immunosorbent assay; CA 15-3 was determined by chemiluminescent microparticle immunoassay. Results: In the group of patients with BC, the area under the curve (AUC) was significantly higher for all markers (except MMP-3) and all sets of markers. At the earliest disease stage, only MMP-10 had a significantly higher AUC (AUC = 0.8692, p < 0.001). Moreover, MMP-10 had the highest AUC (0.9166) among parameters tested separately. The highest AUC was observed for the combination of MMP-10 + CA 15-3 and MMP-3 + MMP-10 + CA 15-3 in line with disease progression (stage I 0.8884 and 0.8906, stage II 0.9244 and 0.9308, stages III + IV 0.9919 and 0.9944, respectively, p < 0.001 in all cases). Conclusions: The results suggest that MMP-10 could be a potential marker in early stages of BC. Moreover, plasma concentration of MMP-10 and MMP-3 in combination with CA 15-3 may improve diagnosis of this type of cancer.


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