Abstract 4852: Collagen degradation products measured in serum can separate ovarian and breast cancer patients from healthy controls

Abstract

Abstract Background: The hallmarks of breast and ovarian cancer include increased matrix metalloproteinase (MMP) activity, increased collagen deposition (desmoplasia) and breakdown, as well as invasion of the basement membrane and extracellular matrix. The combination of these processes result in the release of specific protein (e.g. collagens) fragments to the circulation, which when measured may reflect disease pathogenesis. Aim: To investigate if biomarkers measuring MMP-degraded collagen could differentiate ovarian and breast cancer patients from healthy controls when measured in serum. Methods: The levels of markers reflecting MMP-mediated degradation of type I (C1M), type III (C3M) and type IV (C4M, C4M12) collagen were assessed in serum from female ovarian cancer patients (n=10, stage I-III, age 37-74), breast cancer patients (n=14, stage II-III, age 41-79) and healthy controls (n=49, age 31-83) using characterized and validated competitive ELISAs. The levels of the individual markers were compared using one way ANOVA on log transformed data and AUROC was calculated. Results: The levels of the markers (table) 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. All the markers were able to differentiate ovarian (AUROC 88%-95%) and breast cancer patients (AUROC 70%-88%) from healthy controls, with C1M being the strongest differentiator of disease vs. controls. Conclusions: Four serum biomarkers measuring altered MMP-mediated collagen turnover were able to differentiate ovarian and breast cancer patients from healthy controls in this small cancer cohort study. As these markers reflect altered disease pathogenesis they may increase the understanding of disease mode of action and, if validated in larger clinical studies, provide an improved and additional clinical tool for stratifying and monitoring patients according to subtype/ disease severity. Serum levels of C1M, C3M, C4M and C4M12 in healthy control, ovarian and breast cancer patients.Controls (n=49)Ovarian (n=10)Breast (n=14)Median, ng/ml (range)Median, ng/ml (range)ANOVA (P-value)AUROCMedian, ng/ml (range)ANOVA (P-value)AUROCC1M56.0 (3.0-194.4)372.6 (51.9-451.4)p<0.000195252.2 (20.5-345.5)p<0.000188C3M11.7 (6.0-28.9)29.1 (11.3-40.3)p<0.00018922.0 (10.6-37.2)p<0.000181C4M51.7 (20.5-180.4)108.1 (43.4-223.2)p<0.00018975.8 (40.4-142.5)P=0.000483C4M1238.8 (18.3-95.2)114.6 (31.0-282.6)p<0.00018860.6 (20.2-154.7)P=0.0470 Citation Format: Cecilie L. Bager, Nicholas Willumsen, Diana J. Leeming, Victoria Smith, Morten Karsdal, Anne-Christine B. Jensen. Collagen degradation products measured in serum can separate ovarian and breast cancer patients from healthy controls. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4852. doi:10.1158/1538-7445.AM2014-4852