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Titel: Collagen turnover biomarkers to predict outcome of patients with biliary cancer
VerfasserIn: Kaps, Leonard
Genc, Muhammed A.
Moehler, Markus
Grabbe, Stephan
Schattenberg, Jörn M.
Schuppan, Detlef
Pedersen, Rasmus Sund
Karsdal, Morten A.
Mildenberger, Philipp
Maderer, Annett
Willumsen, Nicholas
Sprache: Englisch
Titel: BMC Gastroenterology
Bandnummer: 25
Heft: 1
Verlag/Plattform: BMC
Erscheinungsjahr: 2025
Freie Schlagwörter: Tumor marker
Extracellular matrix
Gastrointestinal cancer
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Background The collagen-rich tumor stroma plays a crucial role in biliary tract cancer (BTC). Collagen biomarkers of type I collagen (reC1M), type III collagen (PRO-C3), type IV collagen (C4G), type VIII collagen (PRO-C8), type XI collagen (PRO-C11), type XVII collagen (PRO-C17) and type VIII collagen (TUM) may be used as potential non-invasive biomarkers. Methods We measured the seven biomarkers of collagen turnover in sera of 72 patients with BTC at baseline and after frst and second chemotherapy cycle (CTX). Markers were also assessed in sera of 50 healthy controls and compared to levels of patients at baseline. The diagnostic and prognostic value of the markers was evaluated for overall survival (OS) and progression-free survival (PFS). Results Patients had a median age of 65 years (IQR 57–70), while healthy controls were younger, with a median age of 46 years (IQR 38–54). The majority of patients (62%) were diagnosed with intrahepatic bile duct adenocarcinoma. Except C4G, all collagen turnover markers were signifcantly (p<0.001) increased in serum from patients with BTC compared to healthy controls. PRO-C3 was the best marker to discriminate between patients with BTC and controls, reaching an area under a receiver operating characteristic (AUROC) of 0.98 (95% CI 0.95; 0.99) with a sensitivity (92%) and specifcity (94%) balanced cutof of 77.3 ng/ml. Patients with high levels (cohort separated by median split) of PRO-C8 (HR 2.85, 95% CI 1.42; 5.73) followed by C3M (HR 2.33, 95% CI 1.2; 4.5), PRO-C3 (HR 3.09, 95% CI 1.5; 6.36) and CA 19–9 (HR 2.52, 95% CI 1.37; 4.64) as reference biomarker had a shorter OS. Notably, only the novel marker PRO-C8 was also predictive of PFS (HR 3.26, 95% CI 1.53; 6.95). Associations with survival outcomes remained signifcant after adjusting for relevant risk factors (CA 19–9 and CEA at baseline, age, presence of metastases, weight, height and gender). Conclusion The collagen turnover markers PRO-C8, C3M, PRO-C3 and the established biomarker CA 19–9 were prognostic for OS in patients with BTC while only PRO-C8 was also predictive for PFS. PRO-C3 showed the best diagnostic performance to discriminate between patients with BTC and controls. Trial registration Trial registration number and date of registration NCT00661830 (NCT number) 15 April 2008 Trial registry The complete registry can found under: https://clinicaltrials.gov/study/NCT00661830?tab=table#administrative-information (last accessed 01/2025) Principal investigator and study sponsor Markus Moehler, MD Johannes Gutenberg University Mainz
DOI der Erstveröffentlichung: 10.1186/s12876-025-03645-0
URL der Erstveröffentlichung: https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-025-03645-0
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-443986
hdl:20.500.11880/39663
http://dx.doi.org/10.22028/D291-44398
ISSN: 1471-230X
Datum des Eintrags: 14-Feb-2025
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Information
In Beziehung stehendes Objekt: https://static-content.springer.com/esm/art%3A10.1186%2Fs12876-025-03645-0/MediaObjects/12876_2025_3645_MOESM1_ESM.docx
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Innere Medizin
Professur: M - Keiner Professur zugeordnet
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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