High serum levels of the C-propetide of type V collagen (PRO-C5) are prognostic for short overall survival in patients with pancreatic ductal adenocarcinoma.

Autor: Nissen NI; Nordic Bioscience A/S, Herlev, Denmark., Johansen AZ; Department of Oncology, Copenhagen University Hospital, Gentofte, Denmark., Chen IM; Department of Oncology, Copenhagen University Hospital, Gentofte, Denmark., Jensen C; Nordic Bioscience A/S, Herlev, Denmark., Madsen EA; Nordic Bioscience A/S, Herlev, Denmark., Hansen CP; Department of Surgery, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Thorlacius-Ussing J; Nordic Bioscience A/S, Herlev, Denmark., Karsdal M; Nordic Bioscience A/S, Herlev, Denmark., Johansen JS; Department of Oncology, Copenhagen University Hospital, Gentofte, Denmark.; Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Medicine, Copenhagen University Hospital, Gentofte, Denmark., Diab HMH; Digestive Disease Center, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark., Jørgensen LN; Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Digestive Disease Center, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark., Willumsen N; Nordic Bioscience A/S, Herlev, Denmark.
Jazyk: angličtina
Zdroj: Frontiers in molecular biosciences [Front Mol Biosci] 2023 Mar 10; Vol. 10, pp. 1158058. Date of Electronic Publication: 2023 Mar 10 (Print Publication: 2023).
DOI: 10.3389/fmolb.2023.1158058
Abstrakt: Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a pronounced fibrotic tumor microenvironment, which impairs treatment response. Type I and V collagens are responsible for the densely packed fibrils in the tumor fibrosis environment. While the role of the major type I collagen in cancer is well described, less is known about the minor type V collagen. Quantifying collagen propeptides in serum has been shown to have prognostic and predictive value. In this study, we evaluated the clinical utility of measuring the propeptide of type V collagen (PRO-C5) in serum from a discovery cohort and a validation cohort of patients with PDAC as well as in non-pancreatic solid tumor types to explore the relevance of the PRO-C5 biomarker in cancer. Methods: Serum PRO-C5 was measured in three cohorts: a discovery cohort (19 healthy controls, 12 patients with chronic pancreatitis and 33 patients with PDAC (stage I-IV)), a validation cohort (800 patients with PDAC (stage I-IV)), and a non-pancreatic solid tumor type cohort of 33 healthy controls and 200 patients with 10 different non-pancreatic solid tumor types. The levels of serum PRO-C5 in patients with cancer were compared to levels in healthy controls. The association between PRO-C5 levels and overall survival (OS) was evaluated in patients with PDAC after adjusting for established prognostic factors. Results: PRO-C5 was significantly increased in serum from patients with PDAC compared to healthy controls ( p < 0.001). High PRO-C5 levels were significantly associated with short OS in both the discovery- and the validation cohort, especially in early stages of PDAC (validation cohort stage II, HR = 2.0, 95%CI1.2-3.4). The association was independent of other prognostic parameters including stage, performance status and CA19-9. Furthermore, serum levels of PRO-C5 were significantly increased in serum from patients with other non-pancreatic solid tumor types compared to healthy controls. Conclusion: High levels of serum PRO-C5 is prognostic for short OS in patients with PDAC and may provide clinical value in many other tumor types beyond PDAC. This underlines the importance of type V collagen in tumor fibrosis. PRO-C5 could have the potential to be used in several aspects within drug discovery, patient stratification and drug efficacy.
Competing Interests: NN, CJ, EM, JT-U, MK, and NW are all employed by Nordic Bioscience A/S. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Nissen, Johansen, Chen, Jensen, Madsen, Hansen, Thorlacius-Ussing, Karsdal, Johansen, Diab, Jørgensen and Willumsen.)
Databáze: MEDLINE