Oncotarget

Research Papers:

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

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 and Glen Kristiansen _

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Oncotarget. 2016; 7:1421-1438. https://doi.org/10.18632/oncotarget.6370

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Abstract

Sebastian Meller1,*, Hellmuth-A Meyer2,*, Bianca Bethan3, Dimo Dietrich1, Sandra González Maldonado3, Michael Lein4,5, Matteo Montani6, Regina Reszka7, Philipp Schatz7, Erik Peter3, Carsten Stephan4,8, Klaus Jung4,8, Beate Kamlage3,** and Glen Kristiansen1,**

1 Institute of Pathology, University Hospital of Bonn, Bonn, Germany

2 Campus Wilhelminenhof, University of Applied Sciences, Berlin, Germany

3 Metanomics GmbH, Berlin, Germany

4 Berlin Institute for Urologic Research, Berlin, Germany

5 Department of Urology, University Teaching Hospital, Offenbach, Germany

6 Institute of Pathology, University of Bern, Bern, Switzerland

7 Metanomics Health GmbH, Berlin, Germany

8 Department of Urology, University Hospital Charité, Berlin, Germany

* Joint first authors

** Joint senior authors

Correspondence to:

Glen Kristiansen, email:

Keywords: prostate cancer, metabolites, ERG translocation, cholesterol, fatty acid

Received: July 14, 2015 Accepted: November 15, 2015 Published: November 23, 2015

Abstract

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.


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