Identification of novel plasma proteomic biomarkers of Dupuytren disease

TL;DR

This study identifies new blood-based protein markers for Dupuytren disease, which could help in diagnosing and staging the condition.

Contribution

The study introduces novel diagnostic proteomic risk scores and shows that collagen I accumulation in DD is due to impaired degradation.

Findings

Impaired Collagen I degradation, not increased synthesis, causes collagen accumulation in DD.

68 proteins showed significant differences between DD and healthy controls.

DPRS models achieved 76.5% and 70.6% accuracy in distinguishing DD from controls.

Abstract

Dupuytren Disease (DD) is a chronic progressive disease that can cause disabling hand deformities. The most common treatments have either high complication rates or high early recurrence rates. Dupuytren lacks a staging biomarker profile to inform the development of preventive therapeutics to improve long-term outcomes. This multi-omic study aimed to create a DD blood proteomic biomarker profile by comparing DD plasma with that of 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 that showed statistically significant differences compared with 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 hypothesis-based DPRS distinguished Dupuytren from control subjects with accuracies of 76.5% and 70.6%, respectively. Our hypothesis-based DPRS also distinguished DD subjects with different disease progression rates by age at their first corrective procedure (p = 0.0018). This pilot study is the first to provide evidence to suggest that Collagen I accumulation in DD results from 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.

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