Fusion makes a difference – also in the prostate!

ansattebilde.may-britt.tessemailin falkmo hansenBloggers:  Ailin Falkmo Hansen (PhD candidate) and May-Britt Tessem (Research Scientist), MR Cancer group

 

Movember is around with a “trøndersk” spirit on Facebook, Instagram, and the city is filled with mustaches in different shapes and varieties. The goal is increased awareness of men’s health and prostate cancer – a disease we in the MR cancer group want to understand better.

vevsbit og MR

Prostate tissue samples are stored in liquid nitrogen prior to MR spectroscopy analyses (photo: Geir Mogen/NTNU)

How can cancer metabolism provide important information about prostate cancer?

Scientists around the world have shown that changes in metabolism are important characteristics of cancer. We have studied how metabolism is altered due to cancer and how metabolism is changed owing to cancer aggressiveness. Previously, we have found that the two molecules citrate and spermine may be markers for prostate cancer and also can reveal information about aggressiveness.

Prostate cancer is a heterogeneous type of cancer, and this is of importance for treatment and prognosis of patients. However, today there are no reliable methods for assessment of type of prostate cancer. Researchers world-wide are therefore searching for new methods that may provide diagnostic and/or prognostic information. Presence of the fusion gene TMPRSS2-ERG have been suggested to be a candidate method for risk stratification, and in a recently published study we investigated the link between prostate cancer metabolism and TMPRSS2-ERG.

What is a fusion gene and what role does it play in prostate cancer?

TMPRSS2-ERG is a fusion gene that occurs when two genes fuses together. Fusion genes may lead to altered properties of the cancer. For example, TMPRSS2-ERG has been shown to be linked to uncontrolled cell growth and development of prostate cancer. We therefore investigated how metabolism was affected by presence of the TMPRSS2-ERG fusion gene.

In this study, prostate tissue collected through the Regional Research biobank Central Norway, Biobank1 and samples from the MR biobank were used for validation. Comparing samples, with and without fusion gene, revealed several changes in metabolism. Especially interesting were changes in citrate and spermine – these were the two molecules that could distinguish aggressive from less aggressive cancer! The genetic data supported our findings, and our combined results suggested that patients with the fusion gene have a different metabolism profile compared to patients without the fusion gene. Changes could be seen both at gene and metabolism level, see the figure. The fusion gene was especially important for determining the metabolism in “low risk” prostate cancer patients.

Figure

Gene- and metabolic data suggests TMPRSS2-ERG to be linked with altered metabolism, e.g. lower levels of spermine. Lower levels of spermine have previously been linked to more aggressive prostate cancer. Spermine is part of the polyamine pathway and analysis of expression levels of genes in the polyamine pathway reveals alterations of several central genes. ODC1: ornithine decarboxylase 1, SRM: spermidine synthase, SMS: spermine synthase, SAT1: spermidine/spermine N1-acetyltransferase 1 (blue = down-regulated, red=up-regulated).

Our results were validated in another group of patients and levels of the most important changes in metabolites were confirmed in a small group of in vivo MRI patient examinations before surgery of the prostate. Also here, we could see the same differences as we detected in tissue samples, providing a translational potential.

Currently, there is an ongoing discussion whether patients with the fusion gene have a more aggressive prostate cancer than patients without this gene. Although the importance of TMPRSS2-ERG is debatable, our study suggests that patients with the fusion gene comprise an important subgroup of prostate cancer patients. Especially, among patients characterized as “low-risk” it seems interesting to know if the patient has the fusion gene or not.

We gratefully acknowledge the funding from the Cancer Society.

 

Reference: A.F. Hansen, E. Sandsmark, M.B. Rye, A.J. Wright, H. Bertilsson, E. Richardsen, T. Viset, A.M. Bofin, A. Angelsen, K.M. Selnæs, T.F. Bathen, M.-B. Tessem, Presence of TMPRSS2-ERG is associated with alterations of the metabolic profile in human prostate cancer, 2016.

 

This post is also available in: Norwegian Bokmål

Leave a Comment

Filed under Cancer, NTNUmedicine, Research