The genes controlling normal function of citrate and spermine secretion are lost in aggressive prostate cancer and prostate model systems
Morten Beck Rye,
Sebastian Krossa,
Martina Hall,
Casper van Mourik,
Tone F. Bathen,
Finn Drabløs,
May-Britt Tessem,
Helena Bertilsson
Affiliations
Morten Beck Rye
Department of Clinical and Molecular Medicine, NTNU – Norwegian University of Science and Technology, P.O. Box 8905, 7491 Trondheim, Norway; Clinic of Surgery, St.Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway; Clinic of Laboratory Medicine, St.Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway; BioCore - Bioinformatics Core Facility, NTNU – Norwegian University of Science and Technology, P.O. Box 8905, 7491 Trondheim, Norway; Corresponding author
Sebastian Krossa
Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway
Martina Hall
Department of Biotechnology and Food Science, NTNU – Norwegian University of Science and Technology, Trondheim, Norway; K. G. Jebsen Center for Genetic Epidemiology, NTNU – Norwegian University of Science and Technology, Trondheim, Norway
Casper van Mourik
Department of Clinical and Molecular Medicine, NTNU – Norwegian University of Science and Technology, P.O. Box 8905, 7491 Trondheim, Norway; Institute for Life Science & Technology, Hanze University of Applied Sciences, 9747 AS Groningen, the Netherlands
Tone F. Bathen
Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway
Finn Drabløs
Department of Clinical and Molecular Medicine, NTNU – Norwegian University of Science and Technology, P.O. Box 8905, 7491 Trondheim, Norway
May-Britt Tessem
Clinic of Surgery, St.Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway; Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway
Helena Bertilsson
Department of Clinical and Molecular Medicine, NTNU – Norwegian University of Science and Technology, P.O. Box 8905, 7491 Trondheim, Norway; Clinic of Surgery, St.Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
Summary: High secretion of the metabolites citrate and spermine is a unique hallmark for normal prostate epithelial cells, and is reduced in aggressive prostate cancer. However, the identity of the genes controlling this biological process is mostly unknown. In this study, we have created a gene signature of 150 genes connected to citrate and spermine secretion in the prostate. We have computationally integrated metabolic measurements with multiple transcriptomics datasets from the public domain, including 3826 tissue samples from prostate and prostate cancer. The accuracy of the signature is validated by its unique enrichment in prostate samples and prostate epithelial tissue compartments. The signature highlights genes AZGP1, ANPEP and metallothioneins with zinc-binding properties not previously studied in the prostate, and the expression of these genes are reduced in more aggressive cancer lesions. However, the absence of signature enrichment in common prostate model systems can make it challenging to study these genes mechanistically.
