title: Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer.
abstract: Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a great potential for cancer. Levels of matrix metalloproteinase (MMP) generated fragments of type I collagen (C1M), of elastin (ELM), and of citrullinated vimentin (VICM) were measured in serum from patients with lung cancer (n = 40), gastrointestinal cancer (n = 25), prostate cancer (n = 14), malignant melanoma (n = 7), chronic obstructive pulmonary disease (COPD) (n = 13), and idiopathic pulmonary fibrosis (IPF) (n = 10), as well as in age-matched controls (n = 33). The area under the receiver operating characteristics (AUROC) was calculated and a diagnostic decision tree generated from specific cutoff values. C1M and VICM were significantly elevated in lung cancer patients as compared with healthy controls (AUROC = 0.98, P < 0.0001) and other cancers (AUROC = 0.83 P < 0.0001). A trend was detected when comparing lung cancer with COPD+IPF. No difference could be seen for ELM. Interestingly, C1M and VICM were able to identify patients with lung cancer with a positive predictive value of 0.9 and an odds ratio of 40 (95% CI = 8.7-186, P < 0.0001). Biomarkers specifically reflecting degradation of collagen type I and citrullinated vimentin are applicable for lung cancer patients. Our data indicate that biomarkers reflecting ECM and IMF protein dysregulation are highly applicable in the lung cancer setting. We speculate that these markers may aid in diagnosing and characterizing patients with lung cancer.
authors.affiliation: Biomarkers & Research, Nordic Bioscience A/S, DK-2730, Herlev, Denmark.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Willumsen
authors.forename: Cecilie L
authors.initials: CL
authors.lastname: Bager
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
authors.forename: Victoria
authors.initials: V
authors.lastname: Smith
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.forename: David
authors.initials: D
authors.lastname: Dornan
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Bay-Jensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014746:Vimentin / Q000097:blood / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D014746:Vimentin
keywords: Extracellular matrix; lung cancer; protein fingerprint; remodeling; serum biomarkers; tumor tissue