title: Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients.
abstract: During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of protein fragments of collagen type I, III and IV as novel biomarkers for colorectal cancer. Specific fragments of degraded type I, III and IV collagen (C1M, C3M, C4M) and type III collagen formation (Pro-C3) were assessed in serum from colorectal cancer patients, subjects with adenomas and matched healthy controls using well-characterized and validated ELISAs. Serum levels of the biomarkers were significantly elevated in colorectal cancer patients compared to subjects with adenomas (C1M, Pro-C3, C3M) and controls (C1M, Pro-C3). When patients were stratified according to their tumour stage, all four biomarkers were able to differentiate stage IV metastatic patients from all other stages. Combination of all markers with age and gender in a logistic regression model discriminated between metastatic and non-metastatic patients with an AUROC of 0.80. The data suggest that the levels of these collagen remodeling biomarkers may be a measure of tumour activity and invasiveness and may provide new clinical tools for monitoring of patients with advanced stage colorectal cancer.
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark.|Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Denmark.
authors.forename: S N
authors.initials: SN
authors.lastname: Kehlet
authors.affiliation: Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL and CIBERESP, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Sanz-Pamplona
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Brix
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: D J
authors.initials: DJ
authors.lastname: Leeming
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark.
authors.forename: M A
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Unit of Biomarkers and Susceptibility, Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL and CIBERESP, Hospitalet de Llobregat, Barcelona, Spain.|Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Moreno
mesh_terms: D000236:Adenoma / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D003094:Collagen / Q000097:blood / Q000378:metabolism*; D024042:Collagen Type I / Q000097:blood / Q000378:metabolism; D024061:Collagen Type III / Q000097:blood / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D024042:Collagen Type I; D024061:Collagen Type III; D003094:Collagen