title: Integration of tissue metabolomics, transcriptomics and immunohistochemistry reveals ERG- and gleason score-specific metabolomic alterations in prostate cancer.
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.
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Meller
authors.affiliation: Campus Wilhelminenhof, University of Applied Sciences, Berlin, Germany.
authors.forename: Hellmuth-A
authors.initials: HA
authors.lastname: Meyer
authors.affiliation: Metanomics GmbH, Berlin, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Bethan
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Dimo
authors.initials: D
authors.lastname: Dietrich
authors.affiliation: Metanomics GmbH, Berlin, Germany.
authors.forename: Sandra González
authors.initials: SG
authors.lastname: Maldonado
authors.affiliation: Berlin Institute for Urologic Research, Berlin, Germany.|Department of Urology, University Teaching Hospital, Offenbach, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lein
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Montani
authors.affiliation: Metanomics Health GmbH, Berlin, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Reszka
authors.affiliation: Metanomics Health GmbH, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schatz
authors.affiliation: Metanomics GmbH, Berlin, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Peter
authors.affiliation: Berlin Institute for Urologic Research, Berlin, Germany.|Department of Urology, University Hospital Charité, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.affiliation: Berlin Institute for Urologic Research, Berlin, Germany.|Department of Urology, University Hospital Charité, Berlin, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.affiliation: Metanomics GmbH, Berlin, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Kamlage
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D030541:Databases, Genetic; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D060787:Neoplasm Grading; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010084:Oxidation-Reduction; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018511:Systems Integration; D000071230:Transcriptional Regulator ERG / Q000235:genetics; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C072312:ERG protein, human; D005227:Fatty Acids; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D000071230:Transcriptional Regulator ERG; D002784:Cholesterol
keywords: ERG translocation; cholesterol; fatty acid; metabolites; prostate cancer