The genes controlling normal function of citrate and spermine secretion are lost in aggressive prostate cancer and prostate model systems
Rye, Morten Beck; Krossa, Sebastian; Hall, Martina; van Mourik, Casper; Bathen, Tone Frost; Drabløs, Finn; Tessem, May-Britt; Bertilsson, Helena
Peer reviewed, Journal article
Published version
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https://hdl.handle.net/11250/3050660Utgivelsesdato
2022Metadata
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- Institutt for bioteknologi og matvitenskap [1588]
- Institutt for klinisk og molekylær medisin [3578]
- Institutt for samfunnsmedisin og sykepleie [3704]
- Institutt for sirkulasjon og bildediagnostikk [1924]
- Publikasjoner fra CRIStin - NTNU [38484]
- Publikasjoner fra Cristin - St. Olavs hospital [1590]
- St. Olavs hospital [2558]
Sammendrag
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.