Urinary peptide analysis differentiates pancreatic cancer from chronic pancreatitis

Schönemeier, B. et al. (2016) Urinary peptide analysis differentiates pancreatic cancer from chronic pancreatitis. Pancreas, 45(7), pp. 1018-1026. (doi: 10.1097/mpa.0000000000000573) (PMID:26784907)

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Abstract

Objectives: Differentiation of pancreatic cancer (PCA) from chronic pancreatitis (CP) is challenging. We searched for peptide markers in urine to develop a diagnostic peptide marker model. Methods: Capillary electrophoresis–mass spectrometry was used to search for peptides in urine of patients with PCA (n = 39) or CP (n = 41). Statistical different peptides were included in a peptide multimarker model. Peptide markers were sequence identified and validated by immunoassay and immunohistochemistry (IHC). Results: Applied to a validation cohort of 54 patients with PCA and 52 patients with CP, the peptide model correctly classified 47 patients with PCA and 44 patients with CP (area under the curve, 0.93; 87% sensitivity; 85% specificity). All 5 patients with PCA with concomitant CP were classified positive. Urine proteome analysis outperformed carbohydrate antigen 19-9 (area under the curve, 0.84) by a 15% increase in sensitivity at the same specificity. From 99 healthy subjects, only four were misclassified. Fetuin-A was the most prominent peptide marker source for PCA as verified by immunoassay and IHC. In silico protease mapping of the peptide markers' terminal sequences pointed to increased meprin-A activity in PCA, which in IHC was associated with neoangiogenesis. Conclusions: Urinary proteome analysis differentiates PCA from CP and may serve as PCA screening tool.

Item Type:Articles
Additional Information:This study was supported by the German Walter Schulz Stiftung to Tim O. Lankisch and in part by the grant 260844 from the HEPACUTE EU-project to Jochen Metzger and Harald Mischak. Julie Klein acknowledges ERA-EDTA (ALTF 82-2011) and Marie-Curie (ProteasiX, 300582 from FP7-PEOPLE-2011-IEF) for their financial support in the development of Proteasix.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mullen, Dr Bill and Husi, Dr Holger and Mischak, Professor Harald
Authors: Schönemeier, B., Metzger, J., Klein, J., Husi, H., Bremer, B., Armbrecht, N., Dakna, M., Schanstra, J. P., Rosendahl, J., Wiegand, J., Jäger, M., Mullen, W., Breuil, B., Plentz, R. R., Lichtinghagen, R., Brand, K., Kühnel, F., Mischak, H., Manns, M. P., and Lankisch, T. O.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Pancreas
Publisher:Lippincott, Williams & Wilkins
ISSN:0885-3177
ISSN (Online):1536-4828

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