Plasma levels of the MMP-9:TIMP-1 complex as prognostic biomarker in breast cancer: a retrospective study
| Autor: | Anne-Sofie Schrohl, Stine Buch Thorsen, Martin Lundberg, Jan Stenvang, Mick Knowles, Lena Vinther, Birgitte Nielsen, Nils Brünner, Nick Gee, Sidse Ørnbjerg Würtz, Simon Fredriksson, Sarah Lt Christensen, Susanne Møller |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Oncology
medicine.medical_specialty Pathology Cancer Research medicine.medical_treatment Plasma MMP-9:TIMP-1 complex Breast Neoplasms Enzyme-Linked Immunosorbent Assay Matrix metalloproteinase Proximity ligation assay Disease-Free Survival Breast cancer Surgical oncology Limit of Detection Internal medicine medicine Adjuvant therapy Carcinoma Genetics Biomarkers Tumor Humans Aged Proportional Hazards Models Retrospective Studies Chemotherapy Tissue Inhibitor of Metalloproteinase-1 business.industry Proportional hazards model Carcinoma Ductal Breast Retrospective cohort study Middle Aged Reference Standards medicine.disease Prognosis Matrix Metalloproteinase 9 Multivariate Analysis Disease Progression ELISA Female business Blood Chemical Analysis Research Article |
| Zdroj: | BMC Cancer |
| ISSN: | 1471-2407 |
| Popis: | Background Worldwide more than one million women are annually diagnosed with breast cancer. A considerable fraction of these women receive systemic adjuvant therapy; however, some are cured by primary surgery and radiotherapy alone. Prognostic biomarkers guide stratification of patients into different risk groups and hence improve management of breast cancer patients. Plasma levels of Matrix Metalloproteinase-9 (MMP-9) and its natural inhibitor Tissue inhibitor of metalloproteinase-1 (TIMP-1) have previously been associated with poor patient outcome and resistance to certain forms of chemotherapy. To pursue additional prognostic information from MMP-9 and TIMP-1, the level of the MMP-9 and TIMP-1 complex (MMP-9:TIMP-1) was investigated in plasma from breast cancer patients. Methods Detection of protein:protein complexes in plasma was performed using a commercially available ELISA kit and, for the first time, the highly sensitive in-solution proximity ligation assay (PLA). We screened plasma from 465 patients with primary breast cancer for prognostic value of the MMP-9:TIMP-1 complex. Both assays were validated and applied for quantification of MMP-9:TIMP-1 concentration. In this retrospective study, we analyzed the association between the concentration of the MMP-9:TIMP-1 complex and clinicopathological data and disease free survival (DFS) in univariate and multivariate survival analyses. Results Following successful validation both assays were applied for MMP-9:TIMP-1 measurements. Of the clinicopathological parameters, only menopausal status demonstrated significant association with the MMP-9:TIMP-1 complex; P = 0.03 and P = 0.028 for the ELISA and PLA measurements, respectively. We found no correlation between the MMP-9:TIMP-1 protein complex and DFS neither in univariate nor in multivariate survival analyses. Conclusions Despite earlier reports linking MMP-9 and TIMP-1 with prognosis in breast cancer patients, we here demonstrate that plasma levels of the MMP-9:TIMP-1 protein complex hold no prognostic information in primary breast cancer as a stand-alone marker. We demonstrate that the highly sensitive in-solution PLA can be employed for measurements of protein:protein complexes in plasma. |
| Databáze: | OpenAIRE |
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