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