Type VI collagen (COL6) is emerging as an important component of the tumor microenvironment. The rationale that COL6 derived protein fragments may possess pro-tumorigenic properties has ample precedent (e.g. endothrophin). Little is however known, regarding COL6 degradation fragments as biomarkers for cancer. Here we address the biomarker potential of three specific COL6 degradation fragments measured in serum: Pro-C6 (C-terminal of the α3 chain/endotrophin), C6Ma3 (MMP-generated neo-epitope on the α3 chain), C6M (MMP-generated neo-epitope on the α1 chain).
Pro-C6, C6Ma3 and C6M were measured by validated competitive ELISAs in serum from patients with various stage solid tumors prior to treatment and healthy controls (table).
C6M and C6Ma3 were significantly elevated (Kruskal-Wallis test) in most cancer types compared to controls, whereas Pro-C6 was not (table). A trend (p = 0.098) toward higher Pro-C6 was seen in the late (3/4) vs early (1/2) stage (Mann-Whitney test), whereas no difference was seen with C6M (p = 0.822) and C6Ma3 (p = 0.458). AUROC was 0.89 (p
Specific type VI collagen fragments were increased in serum from cancer patients compared to healthy controls, and showed promising clinical accuracy. This clearly support COL-6 remodeling/degradation as an important component in understanding tumorgenesis. Future studies will determine biological and clinical applicability of quantifying various COL-6 fragments in serum in relation to cancer.
Clinical trial identification
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A. Wardak, N. Willumsen, D.J. Mogensen, S.H. Nielsen, C. Jensen, S. Kehlet, M.A. Karsdal: Employed by Nordic Bioscience involved in biomarker development