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The following is a summary of “Collagen turnover biomarkers to predict outcome of patients with biliary cancer,” published in the February 2025 issue of Gastroenterology by Kaps et al.

Researchers conducted a retrospective study to evaluate collagen biomarkers (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)) as potential non-invasive biomarkers for biliary tract cancer (BTC). 

They measured 7 collagen turnover biomarkers in the sera of 72 patients with BTC at baseline and after the first and second chemotherapy cycles (CTX). These biomarkers were also assessed in the sera of 50 healthy controls and compared with baseline levels of patients. The diagnostic and prognostic value of the markers was evaluated in relation to overall survival (OS) and progression-free survival (PFS). 

The results showed that patients had a median age of 65 years (IQR 57–70), while healthy controls had a median age of 46 years (IQR 38–54). Most patients (62%) were diagnosed with intrahepatic bile duct adenocarcinoma. All collagen turnover markers, except C4G, were significantly elevated (P < 0.001) in patients with BTC compared to controls, PRO-C3 was the best marker to distinguish patients with BTC, with an an area under a receiver operating characteristic (AUROC) of 0.98 (95% Confidence interval (CI) 0.95; 0.99), sensitivity of 92%, and specificity of 94% at a cutoff of 77.3 ng/ml. Patients with high levels of PRO-C8 (HR 2.85, 95% CI 1.42; 5.73), Fragment generated by MMP-degraded type III collagen (C3M) (HR 2.33, 95% CI 1.2; 4.5), PRO-C3 (HR 3.09, 95% CI 1.5; 6.36), and Carbohydrate antigen 19–9 (CA 19–9) (HR 2.52, 95% CI 1.37; 4.64) had shorter OS, PRO-C8 was also predictive of PFS (HR 3.26, 95% CI 1.53; 6.95). These associations remained significant after adjusting for relevant risk factors such as CA 19–9, Carcinoembryonic antigen (CEA), age, metastases, weight, height, and gender. 

Investigators concluded that collagen turnover markers, particularly PRO-C8, were prognostic for OS in BTC, with PRO-C8 also predictive of PFS, and PRO-C3 demonstrating the best diagnostic performance. 

Source: bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-025-03645-0