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. CONCLUSION: Four serum biomarkers reflecting altered MMP-mediated collagen turnover were able to differentiate ovarian and breast cancer patients from healthy controls.
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 cancerpatients 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 cancerpatients (n= 10), breast cancerpatients (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 cancerpatients (p< 0.0001) and breast cancerpatients (p< 0.04-0.0001) compared to healthy controls. Furthermore, diagnostically the markers were able to differentiate ovarian (AUROC 90%-93%) and breast cancerpatients (AUROC 76%-93%) from healthy controls, with C1M being the strongest differentiator of disease vs. CONCLUSION: Four serum biomarkers reflecting altered MMP-mediated collagen turnover were able to differentiate ovarian and breast cancerpatients from healthy controls.
Authors: Nicholas Willumsen; Cecilie L Bager; Anne-Christine Bay-Jensen; Stephanie N Kehlet; Henrik Harling; Diana J Leeming; Morten A Karsdal; Lars N Jorgensen Journal: Oncol Lett Date: 2017-03-23 Impact factor: 2.967
Authors: Malgorzata Banys-Paluchowski; Sibylle Loibl; Isabell Witzel; Christoph Mundhenke; Bianca Lederer; Christine Solbach; Thomas Karn; Frederik Marmé; Valentina Nekljudova; Christian Schem; Elmar Stickeler; Nicholas Willumsen; Morten A Karsdal; Michael Untch; Volkmar Müller Journal: Cancers (Basel) Date: 2019-08-15 Impact factor: 6.639
Authors: Nicholas Willumsen; Christina Jensen; George Green; Neel I Nissen; Jaclyn Neely; David M Nelson; Rasmus S Pedersen; Peder Frederiksen; Inna M Chen; Mogens K Boisen; Astrid Z Johansen; Daniel H Madsen; Inge Marie Svane; Allan Lipton; Kim Leitzel; Suhail M Ali; Janine T Erler; Daan P Hurkmans; Ron H J Mathijssen; Joachim Aerts; Mohammed Eslam; Jacob George; Claus Christiansen; Mina J Bissel; Morten A Karsdal Journal: Cell Mol Life Sci Date: 2022-03-25 Impact factor: 9.207
Authors: Nicholas Willumsen; Cecilie L Bager; Stephanie N Kehlet; Katrine Dragsbaek; Jesper S Neergaard; Henrik B Hansen; Anne-Christine Bay-Jensen; Diana J Leeming; Allan Lipton; Claus Christiansen; Morten Karsdal Journal: Oncotarget Date: 2017-02-11