title: Plasma Levels and Diagnostic Utility of Macrophage Colony-Stimulating Factor, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinases-1 as New Biomarkers of Breast Cancer.
abstract: BACKGROUND
  Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and its specific tissue inhibitor - tissue inhibitor of metalloproteinases-1 (TIMP-1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M-CSF, MMP-9, and TIMP-1 in comparison with a commonly accepted tumor marker CA 15-3 in breast cancer patients and in control groups.
  
  
  METHODS
  The cohort included 110 breast cancer patients in groups at stages I-IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M-CSF, MMP-9, and TIMP-1 were determined by using ELISA, while CA 15-3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA).
  
  
  RESULTS
  The results showed significant differences in concentrations of the analyzed parameters and in levels of CA 15-3 between the groups of breast cancer patients and the two control groups. Diagnosis using these markers was equal to that using CA 15-3 in terms of sensitivity, predictive values of positive and negativetest results (PPV, NPV) and area under the ROC curve (AUC) in the studied groups. The diagnostic specificities of MMP-9, TIMP-1, M-CSF, and CA 15-3 showed equally high values (95%). The combined use of all tested parameters with CA 15-3 resulted in increased sensitivity, NPV, and AUC, especially in the combination of M-CSF with tumor markers (76%, 64%, and 0.8653).
  
  
  CONCLUSIONS
  These findings suggest the tested parameters are useful in the diagnosis of breast cancer patients (except stage I), when combined with CA 15-3.
authors.affiliation: Department of Biochemical Diagnostics, Medical University, Białystok, Poland. zdb@umb.edu.pl.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Ławicki
authors.affiliation: Laboratory of Esthetic Medicine, Medical University, Białystok, Poland.
authors.forename: Edyta Katarzyna
authors.initials: EK
authors.lastname: Głażewska
authors.affiliation: Department of Biochemical Diagnostics, Medical University, Białystok, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Sobolewska
authors.affiliation: Department of HaematologicalDiagnostics, Medical University, Białystok, Poland.
authors.forename: Grażyna Ewa
authors.initials: GE
authors.lastname: Będkowska
authors.affiliation: Department of Biochemical Diagnostics, Medical University, Białystok, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Szmitkowski
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D009367:Neoplasm Staging; D011044:Poland; D012372:ROC Curve; D012680:Sensitivity and Specificity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D018396:Mucin-1; D019715:Tissue Inhibitor of Metalloproteinase-1; D016173:Macrophage Colony-Stimulating Factor; D020780:Matrix Metalloproteinase 9
keywords: Breast cancer; CA 15-3; M-CSF; MMP-9; TIMP-1