Leonard Kaps, Muhammed A Genc, Markus Möhler, Stephan Grabbe, Shifana C Sadiq, Jörn M Schattenberg, Detlef Schuppan, Rasmus Sund Pedersen, Morten A Karsdal, Philipp Mildenberger, Annett Maderer, Nicholas Willumsen
BackgroundCirculating collagen turnover markers, including reC1M, PRO-C3, C3M, C4G, PRO-C8, TUM, PRO-C11, and PRO-C17, may serve as non-invasive biomarkers in gastric cancer (GC).MethodsEight serum collagen turnover markers were quantified in 74 pretreated GC patients from the SUNCASE trial and compared to 50 healthy donors. Markers were assessed at baseline and longitudinally after the first and second chemotherapy cycle. Diagnostic accuracy was evaluated by AUROC analysis; prognostic value was assessed for overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier and Cox regression analyses.ResultsAll markers except C4G were significantly elevated in GC patients vs. controls (p < 0.001). C3M showed the strongest diagnostic performance (AUROC 0.88, 95% CI 0.81-0.95; sensitivity 78%, specificity 77%). Elevated reC1M (HR 2.70), C3M (HR 2.33), PRO-C11 (HR 2.14), and TUM (HR 2.09) were independently prognostic of shorter OS. None of the established tumor markers (CA 19-9, CEA, CA 72-4) retained prognostic significance. Longitudinally, a >20% reduction in PRO-C3 and PRO-C11 after the first chemotherapy cycle was associated with longer OS.ConclusionCollagen turnover markers reC1M, C3M, TUM, and PRO-C11 are independent prognostic markers for OS in advanced GC. C3M demonstrated the highest diagnostic accuracy in distinguishing GC patients from healthy controls.