Pancreatic carcinoma, pancreatitis, and healthy controls - metabolite models in a three-class diagnostic dilemma

  • Background: Metabolomics as one of the most rapidly growing technologies in the ?-omics?field denotes the comprehensive analysis of low molecular-weight compounds and their pathways. Cancer-specific alterations of the metabolome can be detected by high-throughput massspectrometric metabolite profiling and serve as a considerable source of new markers for the early differentiation of malignant diseases as well as their distinction from benign states. However, a comprehensive framework for the statistical evaluation of marker panels in a multi-class setting has not yet been established. Methods: We collected serum samples of 40 pancreatic carcinoma patients, 40 controls, and 23 pancreatitis patients according to standard protocols and generated amino acid profiles by routine mass-spectrometry. In an intrinsic three-class bioinformatic approach we compared these profiles, evaluated their selectivity and computed multi-marker panels combined with the conventional tumor marker CA 19-9. Additionally, we tested for non-inferiority and superiority to determine the diagnostic surplus value of our multi-metabolite marker panels.  Results: Compared to CA 19-9 alone, the combined amino acid-based metabolite panel had a superior selectivity for the discrimination of healthy controls, pancreatitis, and pancreatic carcinoma patients [Volume under ROC surface (VUS) = 0.891 (95\% CI 0.794 - 0.968)]. Conclusions: We combined highly standardized samples, a three-class study design, a highthroughput mass-spectrometric technique, and a comprehensive bioinformatic framework to identify metabolite panels selective for all three groups in a single approach. Our results suggest that metabolomic profiling necessitates appropriate evaluation strategies and ?despite all its current limitations? can deliver marker panels with high selectivity even in multi-class settings.

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Author:Tim Conrad, A. Leichtle, U. Ceglarek, P. Weinert, C.T. Nakas, J.-M. Nuoffer, J. Kase, H. Witzigmann, J. Thiery, G.M. Fiedler
Document Type:Article
Parent Title (English):Metabolomics
Volume:9
Issue:3
First Page:677
Last Page:687
Year of first publication:2013
DOI:http://dx.doi.org/10.1007/s11306-012-0476-7

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