ABSTRACT
Dupuytren Disease (DD) is a chronic progressive disease that can cause disabling hand deformities. The most common treatments have high rates of complications and early recurrence. Dupuytren lacks a staging biomarker profile to develop preventive therapeutics to improve long-term outcomes. This multi-omic study aimed to create a DD blood proteomic biomarker profile by comparing DD plasma to a healthy control group. We measured circulating collagen metabolism peptides and found normal Collagen I synthesis but impaired Collagen I degradation in DD. We measured 6995 serum protein aptamers and identified 68 proteins with statistically significant differences from the control group. We developed two Diagnostic Proteomic Risk Scores (DPRS) based on hypothesis-free and hypothesis-based analyses. In independent data, our hypothesis-free and the hypothesis-based DPRS distinguished Dupuytren from control subjects with 76.5% and 70.6% accuracy, respectively. Our hypothesis- based DPRS also distinguished DD subjects with different disease progression rates based on subject age at the time of their first corrective procedure (p=0.0018). This pilot study is the first to provide evidence that Collagen I accumulation in DD is due to impaired degradation rather than increased collagen synthesis. It also describes novel DPRS that have potential use as diagnostic and staging biomarker panels for Dupuytren disease.
Competing Interest Statement
These authors declare the following competing interests: Morten Karsdal, Cecilie Bager, and Signe Holm Nielsen are all currently employed by Nordic Bioscience; Morten Karsdal, Cecilie Bager, and Signe Holm Nielsen hold stocks in Nordic Bioscience. The rest of the authors have no conflicts of interest to declare.
Footnotes
Abstract wording replaced "proteins" with "aptamers". Shortened introduction, results, and discussion sections to a total of 4000 words. Updated conflict of interest. Added compliance with guidelines verbiage in methods. Moved some graphics and tables from the main manuscript to supplementary materials. No substantive content changes in the introduction, results, discussion, or methods sections.
