Serological Investigation of the Collagen Degradation Profile of Patients with Chronic Obstructive Pulmonary Disease or Idiopathic Pulmonary Fibrosis

Abstract

In both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), abnormally high collagen remodeling occurs within the lung tissue. Matrix metalloproteinase (MMP)-degraded type I, III, IV, V and VI collagen and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-degraded type III collagen were assessed in serum of patients diagnosed with mild COPD (n = 10) or IPF (n = 30), and healthy controls (n = 15). The collagen degradation markers C1M, C3M, C5M and C6M were significantly elevated in serum of both mild COPD and IPF patients, versus controls. C3A and C4M were only elevated in patients with mild COPD, compared with controls. The most reliable indicators of mild COPD versus controls were: C1M (area under the receiver-operating characteristics (AUROC = 0.94, P < 0.0001), C3M (AUROC = 0.95, P < 0.0001), and C5M (AUROC = 0.95, P < 0.0001). The most reliable markers for the diagnosis of IPF were achieved by C1M (AUROC = 0.90, P < 0.0001) and C3M (AUROC = 0.93, P < 0.0001). Collagen degradation was highly up-regulated in patients with IPF and mild COPD, indicating that degradation fragments of collagens are potential markers of pulmonary diseases. Interestingly, C4M and C3A were only elevated in patients with mild COPD, indicating that these markers could be used to distinguish between the two pathologies.

Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study

“…It is possible that the high levels of C1M, C4M, and VICM in the blood are results of a systemic effect where subjects with a general increased remodeling of the ECM and IF have a higher likelihood of developing cancer. Furthermore, all markers have been found elevated in a number of diseases characterized by ECM remodeling and tissue inflammation and are, therefore, not specific to cancer (7)(8)(9)(36)(37)(38)(39). Finally, it needs to be elucidated if the results of this study can be applied to populations of other ages and ethnic backgrounds and if the biomarkers are more useful for certain types of solid cancer.…”

The wound healing, chronic fibrosis, and cancer progression triad

“…In addition, Col-VI spiked some attention due to its selective expression in some fibrotic conditions (i.e., kidney and myocardial fibrosis) as well as in hepatocellular carcinoma (136). In fact, its level of expression has been recently proposed to serve as a clinical prognostic marker (204,205). Carcinomas that typically present an aggressive progression (i.e., liver and pancreas) are characterized by a large deposition of interstitial FN and collagen.…”

Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study

“…These neoepitopes have been shown to be more accurate diagnostic and prognostic markers for individual fibroproliferative diseases than their protein of origin 10,11 . Previous small point-of-diagnosis studies have suggested that matrix neoepitopes may be elevated in individuals with IPF compared with healthy controls [12][13][14] .…”