Cathepsin-S degraded decorin are elevated in fibrotic lung disorders – development and biological validation of a new serum biomarker

BMC Pulmonary Medicine

S. Brix¹  M. Curran²  C. Brodmerkel²  B. Dasgupta²  M. A. Karsdal³  N. Willumsen³  D.J. Leeming³  S.N. Kehlet³  C.L. Bager⁴ 

[1] Department of Biotechnology and Biomedicine, Technical University of Denmark;Janssen Pharmaceutical Companies of J & J, LLC;Nordic Bioscience A/S;Proscion A/S;

关键词: Decorin;    Cathepsin-S;    Extracellular matrix;    Cancer;    Idiopathic pulmonary fibrosis;    Serum biomarker;   

DOI  :  10.1186/s12890-017-0455-x

来源: DOAJ

【 摘 要 】

Abstract Background Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue homeostasis contributing to extracellular matrix remodeling diseases. Here, we present the development and validation of a competitive enzyme-linked immunosorbent assay (ELISA) quantifying a specific fragment of degraded decorin, which has potential as a novel non-invasive serum biomarker for fibrotic lung disorders. Methods A fragment of decorin cleaved in vitro using human articular cartilage was identified by mass-spectrometry (MS/MS). Monoclonal antibodies were raised against the neo-epitope of the cleaved decorin fragment and a competitive ELISA assay (DCN-CS) was developed. The assay was evaluated by determining the inter- and intra-assay precision, dilution recovery, accuracy, analyte stability and interference. Serum levels were assessed in lung cancer patients, patients with idiopathic pulmonary fibrosis (IPF), patients with chronic obstructive pulmonary disease (COPD) and healthy controls. Results The DCN-CS ELISA was technically robust and was specific for decorin cleaved by cathepsin-S. DCN-CS was elevated in lung cancer patients (p < 0.0001) and IPF patients (p < 0.001) when compared to healthy controls. The diagnostic power for differentiating lung cancer patients and IPF patients from healthy controls was 0.96 and 0.77, respectively. Conclusion Cathepsin-S degraded decorin could be quantified in serum using the DCN-CS competitive ELISA. The clinical data indicated that degradation of decorin by cathepsin-S is an important part of the pathology of lung cancer and IPF.

【 授权许可】

Unknown