Plasma Concentrations of Matrilysins MMP-7 and MMP-26 as Diagnostic Biomarkers in Breast Cancer

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.

Download Full-text

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

10.21203/rs.3.rs-73083/v1 ◽

2020 ◽

Author(s):

Barbara Maria Piskór ◽

Andrzej Przylipiak ◽

Emilia Dąbrowska ◽

Iwona Sidorkiewicz ◽

Marek Niczyporuk ◽

...

Keyword(s):

Breast Cancer ◽

Plasma Levels ◽

Proteolytic Enzymes ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Diagnostic Utility ◽

Breast Cancer Patients ◽

Advanced Stages ◽

Individual Marker ◽

The One

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.

Download Full-text

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

Journal of Clinical Medicine ◽

10.3390/jcm10225452 ◽

2021 ◽

Vol 10 (22) ◽

pp. 5452

Author(s):

Grażyna E. Będkowska ◽

Ewa Gacuta ◽

Monika Zbucka-Krętowska ◽

Paweł Ławicki ◽

Maciej Szmitkowski ◽

...

Keyword(s):

Breast Cancer ◽

Surgical Treatment ◽

Plasma Concentrations ◽

Cancer Recurrence ◽

Breast Cancer Recurrence ◽

Enzyme Linked Immunosorbent Assay ◽

Surgical Removal ◽

Diagnostic Utility ◽

Combined Analysis

Breast cancer is the most common malignancy in women globally. The increasing worldwide incidence of this type of cancer illustrates the challenge it represents for healthcare providers. Therefore, new tumor markers are constantly being sought. The aim of this study was to assess plasma concentrations and the diagnostic power of VEGF in 100 patients with early-stage breast cancer, both before and after surgical treatment and during a three-year follow-up. The control groups included 50 subjects with benign breast tumors (fibroadenoma) and 50 healthy women. The VEGF concentration was determined using enzyme-linked immunosorbent assay (ELISA) and the CA 15-3 concentration was determined by chemiluminescent microparticle immunoassay (CMIA). We observed significantly higher preoperative plasma concentrations of VEGF and CA 15-3 in patients with breast cancer. VEGF, similar to CA 15-3, demonstrated high diagnostic utility in the assessment of the long-term efficacy of surgical removal of the tumor. Determinations of VEGF had the highest diagnostic usefulness in the detection of breast cancer recurrence (SE 40%, SP 92%, PPV 67%, NPV 79%). Additionally, the highest values of SE, NPV and AUC were observed during the combined analysis with CA 15-3 (60%; 84%; 0.7074, respectively). Our study suggests a promising diagnostic utility of VEGF in the early stages of breast cancer and in the evaluation of the efficacy of the surgical treatment of breast cancer as well as the detection of breast cancer recurrence, particularly in a combined analysis with CA 15-3 as a new diagnostic panel.

Download Full-text

Evaluation of Vitamin D-Binding Protein Gene Polymorphism and its Plasma Concentration in Kurdish Patients With Breast Cancer in Sanandaj, Iran

Avicenna Journal of Medical Biochemistry ◽

10.34172/ajmb.2020.13 ◽

2020 ◽

Vol 8 (2) ◽

pp. 89-93

Author(s):

Roya Moloudinia ◽

Gelavij Mahmoodi ◽

Mohammad Abdi ◽

Sabrieh Amini ◽

Shirin Ferdowsi

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Gene Polymorphism ◽

Binding Protein ◽

Plasma Concentrations ◽

Significant Risk ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Case Group ◽

Vitamin D Binding Protein

Background: Several studies have indicated that polymorphism in vitamin D pathway genes is associated with breast cancer (BC) risk. Vitamin D-binding protein (VDBP) is a vital element in the metabolism of the vitamin D. VDBP carries the serum 25(OH) D3 to cells to promote vitamin D biological functions, such as cell proliferation and apoptosis. Missense SNP (rs.7041) is a common polymorphism in VDBP gene, which shows ethnic-specific allele frequencies. Objectives: This study presents the correlation of the rs7041 (Asp432Glu) gene polymorphism and plasma concentrations of VDBP in Kurdish patients with BC in Sanandaj, Iran. Methods: This cross-sectional study included 44 premenopausal BC patients and 44 healthy subjects. Plasma VDBP concentration was measured by enzyme-linked immunosorbent assay (ELISA). The VDBP (rs7041) was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Results: VDBP level was associated with a non-significant risk of BC (P=0.397). Frequencies of individuals with VDBP (rs7041) TT, TG, and GG genotypes were 13.6%, 52.2%, and 34.09% in case group and 11.3%, 79.5%, and 9.9% in control group, respectively. Genotype GG associated with increased susceptibility to developing BC (odds ratio [OR]=5.172, CI: 1.555-17.2, P=0.007). There was a significant reverse correlation between GT genotype and BC (OR=0.282, 95% CI: 0.110-0.722, P=0.008) Conclusion: The changes in the vitamin D pathway may increase susceptibility to develop BC in the Iranian Kurdish population.

Download Full-text

Plasma levels of VEGF-A, VEGF B, and VEGFR-1 and applicability of these parameters as tumor markers in diagnosis of breast cancer

Acta Biochimica Polonica ◽

10.18388/abp.2018_2713 ◽

2018 ◽

Cited By ~ 1

Author(s):

Monika Zajkowska ◽

Emilia Lubowicka ◽

Paweł Malinowski ◽

Maciej Szmitkowski ◽

Sławomir Ławicki

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Predictive Value ◽

Plasma Levels ◽

Plasma Concentrations ◽

Control Group ◽

Breast Cancer Patients ◽

Significant Difference ◽

Vegf Family Members ◽

Test Result

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.

Download Full-text

THE LEVEL OF CYTOKINES IN THE SALIVA OF PATIENTS WITH BREAST CANCER

Problems in oncology ◽

10.37469/0507-3758-2019-65-6-825-831 ◽

2019 ◽

Vol 65 (6) ◽

pp. 825-831

Author(s):

Lyudmila Belskaya ◽

Viktor Kosenok

Keyword(s):

Breast Cancer ◽

Control Group ◽

Early Stages ◽

Promising Tool ◽

Urgent Task ◽

Advanced Stages ◽

New Biomarkers ◽

Histological Verification ◽

Control Study ◽

Biochemical Examination

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.

Download Full-text

Plasma Level of MMP-10 May Be a Prognostic Marker in Early Stages of Breast Cancer

Journal of Clinical Medicine ◽

10.3390/jcm9124122 ◽

2020 ◽

Vol 9 (12) ◽

pp. 4122

Author(s):

Barbara Maria Piskór ◽

Andrzej Przylipiak ◽

Emilia Dąbrowska ◽

Iwona Sidorkiewicz ◽

Marek Niczyporuk ◽

...

Keyword(s):

Breast Cancer ◽

Area Under The Curve ◽

Disease Stage ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Early Stages ◽

Potential Marker ◽

Breast Cancer Biomarkers ◽

Diagnostic Usefulness ◽

Chemiluminescent Microparticle Immunoassay

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.

Download Full-text

Περιεγχειρητική κινητική αγγειορυθμιστικών παραγόντων σε ασθενείς με καρκίνο του μαστού

10.12681/eadd/36972 ◽

2014 ◽

Author(s):

Γεώργιος Γεωργίου

Keyword(s):

Breast Cancer ◽

Breast Adenocarcinoma ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Study Group ◽

Rt Pcr ◽

Altered Expression ◽

Female Patients ◽

Significant Difference ◽

Circulating Levels

Βackground: angiogenesis is seen during the multiple stages of carcinogenesis, aswell as during the process of surgical wound healing, a fact which has led tosubstantial debate over the last decades about the potential impact of surgery upon thefinal outcome of ceratin patients treated for breast cancer.Aim: the present research aims at investigating the potential effect of surgery on theprocess of angiogenesis, by studying a number of factors that are related to the latter,in patients suffering from breast cancer before and after the time of the procedure,whilst comparing these results with those of patients that were operated on their breastfor non-malignant disease.Material-Methods: blood from 10 female patients with breast adenocarcinoma(Study Group) was collected via venipuncture before surgery (labeled as PRO), aswell as on post-operative day 3 (labeled as D3) and day 7 (labeled as D7). Moreover,blood samples were also taken from 6 female patients with fibroadenoma (ControlGroup) before surgery (PRO) and on day 3 afetr surgery (D3). These samples weremeasured for detection of circulating levels of three established angiogenesisbiomarkers using ELISA (Enzyme-Linked ImmunoSorbent Assay): VascularEndothelial Growth Factor-A (VEFG-A), Interleukin-8 (IL-8) and basic FibroblastGrowth factor (bFGF or FGF-2). In addition, circulating transcripts of 84 agiogenesirelatedgenes were determined using RT-PCR (Real Time Polymerase ChainReaction). The two groups of patients were firstly compared to each other regardingtheir results. Also, patients belonging to the Study Group were analized at differenttime points regarding surgery. Finally, the results were investigated againstclinicopathological data and patient outcome.Results: using ELISA we were able to detect increased levels of circulating VEGF-Aand IL-8 in the Study Group patients compared to the Control Group patientspreoperatively (p=0,0381 and p=0,0218 respectively), while for bFGF there was nostatistically significant difference documented. Surgery resulted in a significantincrease in VEGF-A levels on D3 (p=0,0389) and D7 (p=0,0172) as compared toPRO levels. Perioperative kinetics of IL-8 showed a mild trend towards increase,which, however, was not statistically significant. Postoperative levels of bFGF wereslightly increased on D3, but on D7 they were even lower than preoperative values(p=0,0205). Using RT-PCR certain differences between the Study Group and theControl Group were recorded regarding the circulating transcripts of a great numberof angiogenesis-related genes preoperatively: upregulation of VEGF-C, EGF, IL-8,FGF-1, SPHK1, NRP1, LAMA5, COL4A3, TEK, EFNA3, EFNB2. AKT1, ITGB3,THBS1, CCL11, TIMP3 and downregulation of CXCL10. Moreover, mastectomyinduced an altered expression in several key-genes in breast cancer patients:upregulation of THBS1, COL4A3, BAI1, ITGB3 and downregulation of EREG,SERPIFN1, CXCL9, CXCL10, IL1B, CCL2, CXCL1, HIF1A, NOTCH4. Conclusions: patients suffering from breast cancer have a different angiogenic profilein comparison to patients with fibroadenoma, as documented through their differencesin circulating levels of angiogenic factors. These levels are greatly changed after thesurgical procedure. VEGF showed a transient increase, while bFGF initially increasedbut only to finally decrease to levels that were even lower than the preoperative ones.Moreover, mastectomy promoted a shift in the expression pattern of a broad panel ofangiogenesis-related gene transcripts.

Download Full-text

Blood-borne fragments of fibronectin after thermal injury

Blood ◽

10.1182/blood.v77.9.2037.2037 ◽

1991 ◽

Vol 77 (9) ◽

pp. 2037-2041 ◽

Cited By ~ 5

Author(s):

P La Celle ◽

FA Blumenstock ◽

TM Saba

Keyword(s):

Thermal Injury ◽

Proteolytic Enzymes ◽

Tissue Injury ◽

Plasma Concentrations ◽

Vena Cava ◽

Enzyme Linked Immunosorbent Assay ◽

Plasma Fibronectin ◽

Opsonic Activity ◽

Macrophage Phagocytosis ◽

Fibronectin Fragments

Abstract Fibronectin is an adhesive protein that can promote phagocytosis and endothelial cell adhesion. Plasma fibronectin declines following burn in animals and patients, potentially due to its complexing with circulating collagenous debris as well as its rapid binding to sites of tissue injury. Such depletion of fibronectin initiates an opsonic deficiency of the plasma. In view of the sensitivity of fibronectin to proteolytic enzymes, an additional factor that could contribute to the decrease of plasma opsonic activity after burn is the proteolytic fragmentation of fibronectin in the blood. In the current study, we determined if fibronectin fragments appear in the blood of anesthetized rats after a sublethal full-thickness skin burn of 15% to 16% of body surface. Plasma fibronectin concentration was quantified by enzyme- linked immunosorbent assay and the presence of fibronectin fragments in plasma was determined by immunoblot analysis. All blood was collected in an antiprotease mixture to yield final plasma concentrations of 0.15% EDTA, 3mmol/L phenylmethylsulfonyl fluoride, and 3 mmol/L iodoacetate to prevent degradation of fibronectin after sampling. Plasma fibronectin decreased 60% to 70% within 30 minutes post-burn, and this low level lasted for at least 4 hours. Within 30 minutes post- burn, two prominent fragments of fibronectin with a molecular weight of 110 +/- 2.2 kd and 122 +/- 3.3 Kd, respectively, were also detected in the plasma. Peak concentration of these fragments was detected at 60 minutes post-burn, but their level declined by 4 hours. By 4 hours, both bands appeared to resolve into doublets. To rule out the possibility that the fragments of fibronectin detected in the plasma were actually generated by coagulation enzymes activated at the site of peripheral blood sampling, rapid direct inferior vena cava sampling was performed, which also yield the presence of the fragments. Thus, fibronectin fragments exist in the plasma following thermal injury. Because fragments of fibronectin can compete with the intact fibronectin molecule with respect to its ability to stimulate macrophage phagocytosis, such fragments may contribute to altered systemic phagocytic host defense following thermal injury. Furthermore, because fibronectin peptides can compete with matrix fibronectin and impair adhesion of cultured endothelial cells, such circulating fragments may also influence the integrity of the vascular barrier.

Download Full-text

Imatinib Plasma Levels and Its Correlation with Response in Chronic-Phase Chronic Myeloid Leukemia: Experience of One Centre.

Blood ◽

10.1182/blood.v114.22.4284.4284 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4284-4284

Author(s):

J. Valentin Garcia. Gutierrez ◽

Jesús Odriozola ◽

Pilar Herrera ◽

Javier Lopez ◽

Maria Calbacho ◽

...

Keyword(s):

Clinical Outcomes ◽

Plasma Levels ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Plasma Concentrations ◽

Chronic Phase ◽

Control Group ◽

Treatment Optimisation ◽

Number Of Patients

Abstract Abstract 4284 Introduction Imatinib (IM), 400 mg/d. induces durable responses in chronic myeloid leukaemia (CML) in chronic phase (CP). However, although IM-biodisponibility is fairly good, its plasma levels are variable and can not be predicted. Recently, these plasma concentrations have been related both to the dose being administrated and to the cytogenetic and molecular responses. Thus, Imatinib pharmacokinetics could be an issue towards treatment optimisation in CML patients. Recent studies suggest that therapeutic IM plasma levels should be above 1040 ng/dl. Aims To evaluate the association between IM dose and throughout plasma levels with different clinical outcomes. Results In this study, we looked for an association between plasma concentrations and clinical outcomes in 16/86 CML chronic phase patients who did not achieve optimal responses following the European Leukemia Net guidelines (ELN) (table 1). Patients with optimal responses and treated with the same standard doses were also analysed as a control group. Patients receiving doses above 400 mg showed throughout plasma levels considered as appropriate. In 7 of 16 patients (47.5%) not achieving optimal responses (ELN criteria), plasma levels were below the supposed therapeutic ranges. We have found no evidence for a correlation between clinical risk factors at diagnosis and the measurement of optimal plasma levels. Conclusions IM plasma levels are well correlated with IM dose administrated in the patients studied. In almost 50% of patients who did not achieve optimal responses, IM plasma levels were under the ranges considered therapeutic. Probably these are the patients who may benefit of a dose increase. Obviously, to learn more about the practical value of these measurements a longer follow up with a larger number of patients is needed. Disclosures: No relevant conflicts of interest to declare.

Download Full-text