Presence of TMPRSS2-ERG is associated with alterations of the metabolic profile in human prostate cancer.
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.
Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Ailin Falkmo
AF
Hansen
Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Elise
E
Sandsmark
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.|St. Olavs Hospital, Trondheim, Norway.|Department of Urology, St. Olavs Hospital, Trondheim, Norway.
Morten Beck
MB
Rye
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
Alan J
AJ
Wright
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Urology, St. Olavs Hospital, Trondheim, Norway.
Helena
H
Bertilsson
Department of Medical Biology, UiT - The Arctic University of Norway, Tromsø, Norway.
Elin
E
Richardsen
Department of Pathology and Medical Genetics, St. Olavs Hospital, Trondheim, Norway.
Trond
T
Viset
Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Anna M
AM
Bofin
Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Anders
A
Angelsen
Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Kirsten M
KM
Selnæs
Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Tone Frost
TF
Bathen
Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
May-Britt
MB
Tessem
D014408:Biomarkers, Tumor / Q000378:metabolism; D002951:Citrates / Q000737:chemistry; D015331:Cohort Studies; D005227:Fatty Acids / Q000737:chemistry; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012044:Regression Analysis; D012697:Serine Endopeptidases / Q000378:metabolism*; D013096:Spermine / Q000737:chemistry; D000071230:Transcriptional Regulator ERG / Q000378:metabolism
D014408:Biomarkers, Tumor; D002951:Citrates; C072312:ERG protein, human; D005227:Fatty Acids; D000071230:Transcriptional Regulator ERG; D013096:Spermine; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
HR-MAS; MRSI; citrate; metabolomics; spermine