title: Collagen degradation products measured in serum can separate ovarian and breast cancer patients from healthy controls: A preliminary study.
abstract: BACKGROUND
  During cancer the otherwise tightly controlled homeostasis of the extracellular matrix (ECM) is disturbed. The protein composition changes, the ECM stiffens and increased levels of proteases are secreted. The combination of these processes result in release of specific protein fragments (e.g. collagens) to the circulation, which when measured may reflect disease pathogenesis.
  
  
  OBJECTIVE
  To investigate if biomarkers of protease-degraded collagen could differentiate ovarian and breast cancer patients from healthy controls when measured in serum.
  
  
  METHODS
  The levels of markers reflecting MMP-degradation of type I (C1M), type III (C3M) and type IV (C4M, C4M12) collagen were assessed in serum from ovarian cancer patients (n= 10), breast cancer patients (n= 14) and healthy controls (n= 49) using validated ELISAs. The markers were compared using one way ANOVA and AUC was calculated.
  
  
  RESULTS
  All markers were significantly elevated in serum from ovarian cancer patients (p< 0.0001) and breast cancer patients (p< 0.04-0.0001) compared to healthy controls. Furthermore, diagnostically the markers were able to differentiate ovarian (AUROC 90%-93%) and breast cancer patients (AUROC 76%-93%) from healthy controls, with C1M being the strongest differentiator of disease vs.
  
  
  CONCLUSIONS
  Four serum biomarkers reflecting altered MMP-mediated collagen turnover were able to differentiate ovarian and breast cancer patients from healthy controls.
authors.affiliation: Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.
authors.forename: C L
authors.initials: CL
authors.lastname: Bager
authors.affiliation: Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Willumsen
authors.affiliation: Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.
authors.forename: D J
authors.initials: DJ
authors.lastname: Leeming
authors.affiliation: Gilead Sciences Inc., Biology, Foster City, CA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Smith
authors.affiliation: Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.
authors.forename: M A
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Gilead Sciences Inc., Biology, Foster City, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Dornan
authors.affiliation: Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.
authors.forename: A C
authors.initials: AC
authors.lastname: Bay-Jensen
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D016022:Case-Control Studies; D024042:Collagen Type I / Q000097:blood*; D024061:Collagen Type III / Q000097:blood*; D024141:Collagen Type IV / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D024042:Collagen Type I; D024061:Collagen Type III; D024141:Collagen Type IV
keywords: Cancer; biomarkers; breast cancer; collagen; degradation; extracellular matrix; matrix metalloproteinase; ovarian cancer; remodeling; tumor microenvironment