title: Nidogen-1 Degraded by Cathepsin S can be Quantified in Serum and is Associated with Non-Small Cell Lung Cancer.
abstract: Loss of basement membrane (BM) integrity is typically associated with cancer. Nidogen-1 is an essential component of the BM. Nidogen-1 is a substrate for cathepsin-S (CatS) which is released into the tumor microenvironment. Measuring nidogen-1 degraded by CatS may therefore have biomarker potential in cancer. The aim of this study was to investigate if CatS-degraded nidogen-1 was detectable in serum and a possible biomarker for cancer, a pathology associated with disruption of the BM. A competitive enzyme-linked immunosorbent assay (NIC) was developed with a monoclonal mouse antibody specific for a CatS cleavage site on human nidogen-1. Dilution and spiking recovery, inter- and intravariation, as well as accuracy were evaluated. Serum levels were evaluated in patients with breast cancer, small cell lung cancer (SCLC), and non-SCLC (NSCLC) and in healthy controls. The results indicated that the NIC assay was specific for nidogen-1 cleaved by CatS. Inter- and intraassay variations were 9% and 14%, respectively. NIC was elevated in NSCLC as compared to healthy controls (P<.001), breast cancer (P<.01), and SCLC (P<.5). The diagnostic power (area under the receiver operating characteristics) of NIC for NSCLC as compared to all other samples combined was 0.83 (95% confidence interval: 0.71-0.95), P<.0001. In conclusion, nidogen-1 degraded by CatS can be quantified in serum by the NIC assay. The current data strongly suggest that cathepsin-S degradation of nidogen-1 is strongly associated with NSCLC, which needs validation in larger clinical cohorts.
authors.affiliation: Nordic Bioscience A/S, Biomarkers & Research, DK-2730, Herlev, Denmark; University of Southern Denmark, Campusvej 55, DK-5230, Odense M, Denmark. Electronic address: nwi@nordicbioscience.com.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Willumsen
authors.affiliation: Nordic Bioscience A/S, Biomarkers & Research, DK-2730, Herlev, Denmark.
authors.forename: Cecilie L
authors.initials: CL
authors.lastname: Bager
authors.affiliation: Nordic Bioscience A/S, Biomarkers & Research, DK-2730, Herlev, Denmark.
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
authors.affiliation: Nordic Bioscience A/S, Biomarkers & Research, DK-2730, Herlev, Denmark.
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Bay-Jensen
authors.affiliation: Nordic Bioscience A/S, Biomarkers & Research, DK-2730, Herlev, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002403:Cathepsins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D059748:Proteolysis; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C029967:nidogen; D002403:Cathepsins; C028217:cathepsin S