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Collagen degradation products measured in serum can separate ovarian and breast cancer patients from healthy controls: A preliminary study

Article type: Research Article

Authors: Bager, C.L.a; * | Willumsen, N.a | Leeming, D.J.a | Smith, V.b | Karsdal, M.A.a | Dornan, D.b | Bay-Jensen, A.C.a

Affiliations: [a] Nordic Bioscience, Biomarkers and Research, Herlev, Denmark | [b] Gilead Sciences Inc., Biology, Foster City, CA, USA

Correspondence: [*] Corresponding author: Cecilie Liv Bager, Nordic Bioscience A/S, Biomarkers and Research, Herlev Hovedgade 207, DK-2730 Herlev, Denmark. Tel.: +45 44 52 52 15; Fax: +45 44 52 52 51; E-mail:cba@nordicbioscience.com

Keywords: Cancer, extracellular matrix, collagen, biomarkers, breast cancer, ovarian cancer, matrix metalloproteinase, degradation, remodeling, tumor microenvironment

DOI: 10.3233/CBM-150520

Journal: Cancer Biomarkers, vol. 15, no. 6, pp. 783-788, 2015

Published: 2015
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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. controls.

CONCLUSION: Four serum biomarkers reflecting altered MMP-mediated collagen turnover were able to differentiate ovarian and breast cancer patients from healthy controls.

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