Presence of TMPRSS2-ERG is associated with alterations of the metabolic profile in human prostate cancer
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Ailin Falkmo Hansen1, Elise Sandsmark1, Morten Beck Rye2,3,4, Alan J. Wright5, Helena Bertilsson2,4, Elin Richardsen6, Trond Viset7, Anna M. Bofin8, Anders Angelsen1, Kirsten M. Selnæs1, Tone Frost Bathen1, May-Britt Tessem1
1Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
2Department of Cancer Research and Molecular Medicine, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
3St. Olavs Hospital, Trondheim, Norway
4Department of Urology, St. Olavs Hospital, Trondheim, Norway
5Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom
6Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway
7Department of Pathology and Medical Genetics, St. Olavs Hospital, Trondheim, Norway
8Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
May-Britt Tessem, email: [email protected]
Keywords: metabolomics, citrate, spermine, HR-MAS, MRSI
Received: March 11, 2016 Accepted: May 16, 2016 Published: June 03, 2016
TMPRSS2-ERG has been proposed to be a prognostic marker for prostate cancer. The aim of this study was to identify changes in metabolism, genes and biochemical recurrence related to TMPRSS2-ERG by using an integrated approach, combining metabolomics, transcriptomics, histopathology and clinical data in a cohort of 129 human prostate samples (41 patients). Metabolic analyses revealed lower concentrations of citrate and spermine comparing ERGhigh to ERGlow samples, suggesting an increased cancer aggressiveness of ERGhigh compared to ERGlow. These results could be validated in a separate cohort, consisting of 40 samples (40 patients), and magnetic resonance spectroscopy imaging (MRSI) indicated an in vivo translational potential. Alterations of gene expression levels associated with key enzymes in the metabolism of citrate and polyamines were in consistence with the metabolic results. Furthermore, the metabolic alterations between ERGhigh and ERGlow were more pronounced in low Gleason samples than in high Gleason samples, suggesting it as a potential tool for risk stratification. However, no significant difference in biochemical recurrence was detected, although a trend towards significance was detected for low Gleason samples. Using an integrated approach, this study suggests TMPRSS2-ERG as a potential risk stratification tool for inclusion of active surveillance patients.
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