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

• Published in: Journal of cancer research and clinical oncology Vol. 145; no. 2; pp. 383 - 392
• Main Authors: Thorlacius-Ussing, Jeppe, Kehlet, Stephanie Nina, Rønnow, Sarah Rank, Karsdal, Morten Asser, Willumsen, Nicholas
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2019; Springer Nature B.V
• Subjects: Biomarkers; Cancer Research; Cathepsin G; Clinical trials; Elastase; Elastin; Gelatinase B; Hematology; Internal Medicine; Lung cancer; Matrilysin; Matrix metalloproteinase; Medicine; Medicine & Public Health; Metalloproteinase; Non-small cell lung carcinoma; Oncology; Original Article – Cancer Research; Proteinase; Proteinase 3; Proteolysis; Tumorigenesis; MMP; Biomarker; NSCLC; Elastin; Lung cancer; Cathepsin g; Serum; Neutrophil elastase; ECM; Proteinase 3
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-018-2799-x

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.