Repository: Freie Universität Berlin, Math Department

Serum Peptidome Profiling Revealed Platelet Factor 4 as a Potential Discriminating Peptide Associated With Pancreatic Cancer

Fiedler, G. M. and Leichtle, A. and Kase, J. and Baumann, S. and Ceglarek, U. and Felix, K. and Conrad, T. O. F. and Witzigmann, H. and Weimann, A. and Schütte, Ch. and Hauss, J. and Büchler, M. and Thiery, J. (2009) Serum Peptidome Profiling Revealed Platelet Factor 4 as a Potential Discriminating Peptide Associated With Pancreatic Cancer. Clinical Cancer Research, 15 (11). pp. 3812-3819. ISSN 1078-0432

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Official URL: http://dx.doi.org/10.1158/1078-0432.CCR-08-2701

Abstract

Purpose: Mass spectrometry-based serum peptidome profiling is a promising tool to identify novel disease-associated biomarkers, but is limited by preanalytical factors and the intricacies of complex data processing. Therefore, we investigated whether standardized sample protocols and new bioinformatic tools combined with external data validation improve the validity of peptidome profiling for the discovery of pancreatic cancer associated serum markers. Experimental Design: For discovery study, two sets of sera from patients with pancreatic cancer (n=40) and healthy controls (n=40) were obtained from two different clinical centers. For external data validation, we collected an independent set of samples from patients (n=20) and healthy controls (n=20). Magnetic beads (MB) with different surface functionalities were used for peptidome fractionation followed by MALDI-TOF MS. Data evaluation was carried out comparing two different bioinformatic strategies. Following proteome database search the matching candidate peptide was verified by MALDI-TOF MS after specific antibody-based immunoaffinity chromatography and independently confirmed by an ELISA assay. Results: Two significant peaks (m/z 3884; 5959) achieved a sensitivity of 86.3% and specificity of 97.6% for the discrimination of patients and healthy controls in the external validation set. Adding peak m/z 3884 to conventional clinical tumor markers (CA 19-9 and CEA) improved sensitivity and specificity as shown by ROC analysis (AUROCcombined=1.00). Mass spectrometry based m/z 3884 peak identification and following immunological quantitation revealed platelet factor 4 as the corresponding peptide. Conclusions: MALDI-TOF MS based serum peptidome profiling allowed the discovery and validation of platelet factor 4 as a new discriminating marker in pancreatic cancer.

Item Type:Article
Subjects:Mathematical and Computer Sciences > Statistics > Applied Statistics > Medical Statistics
Mathematical and Computer Sciences > Statistics > Mathematical Statistics
Mathematical and Computer Sciences > Artificial Intelligence > Machine Learning
Medicine and Dentistry > Clinical Medicine
Divisions:Department of Mathematics and Computer Science > Institute of Mathematics > Comp. Proteomics Group
Department of Mathematics and Computer Science > Institute of Mathematics
Department of Mathematics and Computer Science > Institute of Mathematics > BioComputing Group
ID Code:155
Deposited By: Tim Conrad
Deposited On:14 Jan 2009 11:51
Last Modified:03 Mar 2017 14:40

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