Integration of tissue metabolomics, transcriptomics and immunohistochemistry reveals ERG- and gleason score- specific metabolomic alterations in prostate cancer.

Integrated analysis of metabolomics, transcriptomics and immunohistochemistry can contribute to a deeper understanding of biological processes altered in cancer and possibly enable improved diagnostic or prognostic tests.

In this study, a set of 254 metabolites was determined by gas-chromatography/liquid chromatography-mass spectrometry in matched malignant and non-malignant prostatectomy samples of 106 prostate cancer (PCa) patients. Transcription analysis of matched samples was performed on a set of 15 PCa patients using Affymetrix U133 Plus 2. 0 arrays. Expression of several proteins was immunohistochemically determined in 41 matched patient samples and the association with clinico-pathological parameters was analyzed by an integrated data analysis. These results further outline the highly deregulated metabolism of fatty acids, sphingolipids and polyamines in PCa. For the first time, the impact of the ERG translocation on the metabolome was demonstrated, highlighting an altered fatty acid oxidation in TMPRSS2-ERG translocation positive PCa specimens. Furthermore, alterations in cholesterol metabolism were found preferentially in high grade tumors, enabling the cells to create energy storage. With this integrated analysis we could not only confirm several findings from previous metabolomic studies, but also contradict others and finally expand our concepts of deregulated biological pathways in PCa.

Oncotarget. 2015 Nov 23 [Epub ahead of print]

Sebastian Meller, Hellmuth-A Meyer, Bianca Bethan, Dimo Dietrich, Sandra González Maldonado, Michael Lein, Matteo Montani, Regina Reszka, Philipp Schatz, Erik Peter, Carsten Stephan, Klaus Jung, Beate Kamlage, Glen Kristiansen

Institute of Pathology, University Hospital of Bonn, Bonn, Germany. , Campus Wilhelminenhof, University of Applied Sciences, Berlin, Germany. , Metanomics GmbH, Berlin, Germany. , Institute of Pathology, University Hospital of Bonn, Bonn, Germany. , Metanomics GmbH, Berlin, Germany. , Berlin Institute for Urologic Research, Berlin, Germany. , Institute of Pathology, University of Bern, Bern, Switzerland. , Metanomics Health GmbH, Berlin, Germany. , Metanomics Health GmbH, Berlin, Germany. , Metanomics GmbH, Berlin, Germany. , Berlin Institute for Urologic Research, Berlin, Germany. , Berlin Institute for Urologic Research, Berlin, Germany. , Metanomics GmbH, Berlin, Germany. , Institute of Pathology, University Hospital of Bonn, Bonn, Germany.

PubMed

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