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dc.contributor.authorRoy, Ren_US
dc.contributor.authorZurakowski, Den_US
dc.contributor.authorWischhusen, Jen_US
dc.contributor.authorFrauenhoffer, Cen_US
dc.contributor.authorHooshmand, Sen_US
dc.contributor.authorKulke, Men_US
dc.contributor.authorMoses, M Aen_US
dc.date.accessioned2015-11-03T15:58:14Z
dc.date.issued2014en_US
dc.identifier.citationRoy, R, D Zurakowski, J Wischhusen, C Frauenhoffer, S Hooshmand, M Kulke, and M A Moses. 2014. “Urinary TIMP-1 and MMP-2 levels detect the presence of pancreatic malignancies.” British Journal of Cancer 111 (9): 1772-1779. doi:10.1038/bjc.2014.462. http://dx.doi.org/10.1038/bjc.2014.462.en
dc.identifier.issn0007-0920en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:23473996
dc.description.abstractBackground: A majority of patients with pancreatic malignancies, including both pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumours (pNETs), present with advanced disease due to a lack of specific symptoms and current diagnostic limitations, making this disease extremely difficult to detect. Our goal was to determine whether urinary matrix metalloproteases (uMMPs) and/or their endogenous inhibitors, urinary tissue inhibitor of metalloproteases (uTIMPs), could be detected in the urine of patients with pancreatic malignancies and whether they may serve as independent predictors of disease status. Methods: Retrospective analyses of urine samples (n=139) from PDAC and pNET patients as well as age- and sex-matched controls were conducted. Urinary MMP-2 and uTIMP-1 levels were determined using ELISA and zymography. Biomarker expression in tumour and normal pancreatic tissues was analysed via immunohistochemistry (IHC). Results: Multivariable logistic regression analyses indicated that, when controlling for age and sex, uMMP-2 (P<0.0001) and uTIMP-1 (P<0.0001) but not uMMP-9, were significant independent predictors for distinguishing between PDAC patients and healthy controls. Our data also indicated that uMMP-2 was an independent predictor of the presence of pNET. In addition, uTIMP-1 levels could differentiate the two cancer groups, PDAC and pNET, respectively. Immunohistochemistry analysis confirmed that MMP-2 and TIMP-1 protein expression is significantly upregulated in PDAC tissue compared with the normal pancreas. Conclusions: Taken together, our results suggest that the detection of uMMP-2 and uTIMP-1 may have diagnostic value in the detection of pancreatic malignancies and that uTIMP-1 may be useful in distinguishing between pancreatic adenocarcinoma and neuroendocrine tumours.en
dc.language.isoen_USen
dc.publisherNature Publishing Groupen
dc.relation.isversionofdoi:10.1038/bjc.2014.462en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453724/pdf/en
dash.licenseLAAen_US
dc.subjectMMP-2en
dc.subjectTIMP-1en
dc.subjecturinary biomarkeren
dc.subjectpancreatic canceren
dc.titleUrinary TIMP-1 and MMP-2 levels detect the presence of pancreatic malignanciesen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalBritish Journal of Canceren
dc.date.available2015-11-03T15:58:14Z
dc.identifier.doi10.1038/bjc.2014.462*


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