Identification of novel plasma proteomic biomarkers of Dupuytren Disease.

Dupuytren Disease (DD) is a chronic progressive disease that can result in 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 proteins and identified 68 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 as diagnostic and staging biomarker panels for Dupuytren disease.