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

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.

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.


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.


Author(s):  
Monika Zajkowska ◽  
Ewa Gacuta ◽  
Emilia Lubowicka ◽  
Maciej Szmitkowski ◽  
Sławomir Ławicki

Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3) is a very important factor which promotes lymphangiogenesis not only in physiological but also in pathological processes in which we can include neoplasia. The aim of this study was to analyze the plasma concentrations and diagnostic utility of this parameter in comparison and in combination with CA 15-3 in breast cancer (BC) patients and in relation to the control groups. The study included 120 breast cancer and 60 control patients (28 with benign breast tumors and 32 healthy women). Plasma levels of VEGFR-3 were determined by an Enzyme-Linked Immunosorbent Assay (ELISA), and those of CA 15-3 by a Chemiluminescent Microparticle Immuno Assay (CMIA). Differences in concentrations of both of the tested parameters were statistically significant when breast cancer patients were compared to the control groups. VEGFR-3 had higher values of sensitivity (SE), specificity (SP), predictive value of a positive (PPV) and negative test result (NPV) in the whole BC group (90%; 98.33%; 99.08%; 83.10%, respectively) and, more importantly, in the early stages of BC, than CA 15-3. VEGFR-3 was also a better parameter in terms of statistically significant Area Under Curve (0.9656) in the whole group and at all BC stages (I-IV), but a maximum range was obtained for the combination of VEGFR-3 and CA 15-3 (0.9710). The combined analysis of VEGFR-3 and CA 15-3 provides hope that a new BC diagnostic panel may be developed in the future.


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 ◽  
Author(s):  
Meng Wang ◽  
Jia Yao ◽  
Yi Zheng ◽  
Yuyao Yao ◽  
Shuqian Wang ◽  
...  

Abstract Studies have suggested that thymidylate (TYMS) polymorphisms are associated with breast cancer. However, inconsistent results were obtained and data from Asian populations are largely lacking. In this study, the relationships between two common TYMS polymorphisms (rs2790 and rs1059394) and the breast cancer risk were evaluated. We also studied the TYMS expression between tumor and para-carcinoma tissues, and the association between TYMS levels and prognosis of breast cancer. This hospital-based study included 434 patients and 450 cancer-free individuals. Genotying was performed using Sequenom Mass-ARRAY. The microarray dataset GSE115144 was downloaded to compare the differences in TYMS expression between tumor and para-carcinoma tissues. The microarray dataset GSE20685 was used to analysis the metastasis free survival (MFS) and overall survival (OS) of patients. The rs2790 polymorphism was related to a higher risk of breast cancer (recessive model: OR=1.50, 95%CI=1.02-2.21, P=0.038) and the C allele of rs1059394 was overrepresented in patients with tumor stage III-IV (heterozygote model: OR=0.60, 95%CI=0.39-0.94, P=0.025; dominant model: OR=0.59, 95%CI=0.39-0.89, P=0.013). The tumor tissues had a higher TYMS expression levels and patients with higher TYMS expression levels had worse OS. Overall, TYMS polymorphism may increase susceptibility to breast cancer in Chinese Han women and TYMS expression levels may be a predictive factor for breast cancer patients.


2020 ◽  
Vol 108 (3) ◽  
pp. 661-670 ◽  
Author(s):  
Anna Mueller‐Schoell ◽  
Lena Klopp‐Schulze ◽  
Werner Schroth ◽  
Thomas Mürdter ◽  
Robin Michelet ◽  
...  

2005 ◽  
Vol 33 (03) ◽  
pp. 381-395 ◽  
Author(s):  
Chun-Kwok Wong ◽  
Yi-Xi Bao ◽  
Eliza Lai-Yi Wong ◽  
Ping-Chung Leung ◽  
Kwok Pui Fung ◽  
...  

Breast cancer is the most common cancer among women worldwide. Discomfort and fatigue are usually arisen from anticancer therapy such as surgery, radiotherapy, chemotherapy, hormonal therapy, or combination therapy, because of the suppressed immunological functions. Yunzhi (Coriolus versicolor) can modulate various immunological functions in vitro, in vivo, and in human clinical trials. Danshen (Salvia miltiorrhiza) has been shown to benefit the circulatory system by its vasodilating and anti-dementia activity. The purpose of this clinical trial was to evaluate the immunomodulatory effects of Yunzhi-Danshen capsules in post-treatment breast cancer patients. Eighty-two patients with breast cancer were recruited to take Yunzhi [50 mg/kg body weight, 100% polysaccharopeptide (PSP)] and Danshen (20 mg/kg body weight) capsules every day for a total of 6 months. EDTA blood samples were collected every 2 months for the investigation of immunological functions. Flow cytometry was used to assess the percentages and absolute counts of human lymphocyte subsets in whole blood. Plasma level of soluble interleukin-2 receptor (sIL-2R) was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that the absolute counts of T-helper lymphocytes (CD4+), the ratio of T-helper (CD4+)/T suppressor and cytotoxic lymphocytes (CD8+), and the percentage and the absolute counts of B-lymphocytes were significantly elevated in patients with breast cancer after taking Yunzhi-Danshen capsules, while plasma sIL-2R concentration was significantly decreased (all p < 0.05). Therefore, the regular oral consumption of Yunzhi-Danshen capsules could be beneficial for promoting immunological function in post-treatment of breast cancer patients.


1989 ◽  
Vol 4 (4) ◽  
pp. 207-214 ◽  
Author(s):  
F. Safi ◽  
I. Kohler ◽  
E. Röttinger ◽  
P. Suhr ◽  
H. G. Beger

In order to assess the utility of the tumor-associated antigen CA15-3 in the diagnosis of breast cancer, this new tumor marker was measured pre-operatively in 1342 patients. This group comprised 509 patients with malignant disease (134 with breast cancer and 375 with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast, 738 with other benign diseases). The results were compared with those for carcino-embryonic antigen (CEA) in the diagnosis of breast cancer. CA15-3 was above the normal limits of 25 U/ml in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. CEA was elevated in 26% of patients with breast cancer (> 3ng/ml). CA15-3 levels were above 50 U/ml in 13% of the breast cancer patients, in 6%) of patients with other malignancies, and in 0.2% of the patients with benign diseases. There was a good correlation between CA 15-3 level and tumor stage in breast cancer. CA 15-3 serum levels were over 50 U/ml in respectively 0%, 2%, 13%, and 73% of the patients with stages I, II, III, and IV. CA 15-3 and CEA were also determined in 671 patients who had received initial curative surgery of breast cancer, and who regularly attended our follow-up clinic. CA15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the post-care period, carcinoma recurred in 205 patients. Of these 73% had CA15-3 concentrations above 25 U/ml, whereas only 50% had CEA values above 3 ng/ml (p< 0.0001). Although neither CA15-3 nor CEA are sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 is superior to CEA in the detection of breast cancer metastases.


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