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Journal of Cancer Research and Clinical Oncology

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22.11.2018 | Original Article – Cancer Research

Non-invasive profiling of protease-specific elastin turnover in lung cancer: biomarker potential

verfasst von: Jeppe Thorlacius-Ussing, Stephanie Nina Kehlet, Sarah Rank Rønnow, Morten Asser Karsdal, Nicholas Willumsen

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2019

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Abstract

Purpose

Elastin is a signature protein of lungs. Increased elastin turnover driven by altered proteolytic activity is an important part of lung tumorigenesis. Elastin-derived fragments have been shown to be pro-tumorigenic, however, little is known regarding the biomarker potential of such elastin fragments. Here, we present an elastin turnover profile by non-invasively quantifying five specific elastin degradation fragments generated by different proteases.

Methods

Elastin fragments were assessed in serum from patients with stage I–IV non-small cell lung cancer (NSCLC) (n = 40) and healthy controls (n = 30) using competitive ELISAs targeting different protease-generated fragments of elastin: ELM12 (generated by matrix metalloproteinase MMP-9 and -12), ELM7 (MMP-7), EL-NE (neutrophil elastase), EL-CG (cathepsin G) and ELP-3 (proteinase 3).

Results

ELM12, ELM7, EL-NE and EL-CG were all significantly elevated in NSCLC patients (n = 40) when compared to healthy controls (n = 30) (ELM12, p = 0.0191; ELM7, p < 0.0001; EL-NE, p < 0.0001; EL-CG, p < 0.0001). ELP-3 showed no significant difference between patients and controls (p = 0.8735). All fragments correlated positively (Spearman, r: 0.69–0.81) when compared pairwise, except ELM12 (Spearman, r: 0.042–0.097). In general, all fragments were detectable across all stages of the disease.

Conclusions

Elastin fragments generated by different proteases are elevated in lung cancer patients compared to healthy controls but differ in their presence. This demonstrates non-invasive biomarker potential of elastin fragments in serum from lung cancer patients and suggests that different pathological mechanisms may be responsible for the elastin turnover, warranting further validation in clinical trials.

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Titel: Non-invasive profiling of protease-specific elastin turnover in lung cancer: biomarker potential
verfasst von: Jeppe Thorlacius-Ussing
Stephanie Nina Kehlet
Sarah Rank Rønnow
Morten Asser Karsdal
Nicholas Willumsen
Publikationsdatum: 22.11.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-018-2799-x

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Non-invasive profiling of protease-specific elastin turnover in lung cancer: biomarker potential

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

Methods

Results

Conclusions

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