Selenium and the prostate: clinical trials on availability to prostate tissue and effects on gene expression

Ellen Kampman’s study showed that selenium is able to induce changes in the expression of a number of genes in the prostate.

  • Topic: Prostate cancer
  • Institution: Wageningen University and Research Centre
  • Country: Netherlands
  • Status: Completed
Researcher: Ellen Kampman

Scientific abstract

(view Plain language abstract)

Background

Prostate cancer is the most common cancer among men in Western communities. Prevention is an important point of interest to reduce the incidence and mortality of prostate cancer.

Selenium has been suggested as a chemopreventive candidate for prostate cancer. The exact mechanisms of chemoprevention by selenium, however, are not fully understood.

The identification of changes in gene expression profiles in prostate tissue may reveal the effects of selenium supplementation and the possible underlying chemopreventive mechanisms.

The aim of our study was therefore to examine the effects of a short-term intervention with selenium or a placebo on gene expression profiles in non-malignant prostate tissue.

Methods

In total, 23 men scheduled for a prostate needle biopsy were randomly assigned to take 300 µg selenized yeast per day (SelenoPrecise®, PharmaNord, n=12) or a placebo (non-selenized yeast, n=11) during a median intervention period of 35 days.

At baseline and after the intervention, prostate tissue and blood samples were collected. RNA was extracted from the prostate biopsy specimens and was processed for gene expression analyses.

After exclusion of prostate biopsies with inadequate RNA yield (n=1), histological evidence of malignancies (n=6) or no tissue available (n=1), biopsies of 15 patients were evaluable for gene expression analyses.

Results

As expected, the levels of serum selenium were increased after intervention in the selenium group (median increase (interquartile range): 1.44 (0.66-1.92) µmol/L), but not in the placebo group (median increase (interquartile range): 0.02 (-0.04-0.18) µmol/L) as compared to baseline values.

Comparisons of individual gene expression profiles before and after intervention and between the two intervention groups revealed that expression of 910 genes changed after the intervention with selenium. In the placebo group, expression changes were observed for 1368 genes.

Pathway analyses showed that the expression of a substantial number of genes involved in inflammatory processes was up-regulated in the placebo group, which might be a result of the repeated series of prostate biopsies or a progressive tumour environment.

Interestingly, expression of these genes was down-regulated after the intervention with selenium, suggesting that selenium, to some extent, might exert anti-inflammatory effects in the prostate.

Furthermore, the expression of epithelial markers (E-cadherin) was increased, while the expression of various mesenchymal (N-cadherin, OB-cadherin, vimentin) markers was decreased after the intervention with selenium. This finding may suggest that selenium is able to interfere in the process of epithelial to mesenchymal transition.

This process is normally involved in physiological processes such as embryogenesis and wound healing, but is also implicated in the progression and metastasis of cancer. Additional experiments are required to confirm this preliminary finding.

Conclusions

Our findings suggest that selenium might induce an anti-inflammatory gene expression profile and interferes in the process of epithelial to mesenchymal transition in non-malignant prostate tissue.

To what extent these effects are able to prevent against inflammation and subsequently prostate cancer warrants further research.

Plain language abstract

Background

Prostate cancer is a very common cancer among elderly men. The prevention of prostate cancer is an important strategy in order to reduce the occurrence of this disease.

It’s been suggested that the development of prostate cancer might be prevented by some specific nutritional and lifestyle factors.

Previous studies showed that the dietary trace element selenium decreased the risk of getting prostate cancer; however, other studies were not able to confirm these findings.

At this moment, it’s not clear whether selenium is indeed able to reduce the risk of getting prostate cancer, and there is little information about the effects of selenium in the prostate.

Hypothesis

We hypothesise that selenium is able to induce changes in the cells of the prostate. The aim of our study was to identify whether these changes might be of relevance for the prevention of prostate cancer.

Methods

For this study, 23 men, who were scheduled for a biopsy or a surgery of the prostate, were asked to take a dietary supplement containing 300 µg selenium per day or a placebo. Prostate tissue and blood were collected at the start and 5 weeks after start of the study.

The effects of the intervention with selenium on gene expression were examined in small pieces of prostate tissue. Gene expression refers to the activity of genes and thereby determines whether a gene is “active” or not. Important processes in all organs and tissues are tightly regulated through the control of gene expression. Using so called microarrays, we were able to measure the expression of more than 19,000 genes in the prostate.

Key findings

The results from our study showed that selenium is able to induce changes in the expression of a number of genes in the prostate. We identified the biological processes in which these genes are normally involved.

Activity of some specific genes that are frequently associated with infection and inflammation was decreased (down-regulated) in men who took selenium.

This finding provides preliminary evidence that selenium might prevent against inflammation in the prostate. To what extent the prevention of inflammation will also result in a decreased risk of prostate cancer remains unclear.

Furthermore, we observed that selenium might be able to interfere in a process during which the characteristics of the prostate cells are subtly changed. Normally, this process occurs during tissue repair and inflammation, but it also plays an important role during the progression and spread of cancer cells.

The relevance of this finding with respect to prostate cancer warrants further research. Therefore, future studies are needed in order to study the possible preventive effects of selenium on inflammation and progression of prostate cancer in more detail.

Grant publications

> Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer

> The prognostic role of the pathological T2 subclassification for prostate cancer in the 2002 Tumour-Nodes-Metastasis staging system

> A single institution experience with biochemical recurrence after radical prostatectomy for tumors that on pathology are of small volume or “insignificant”

> Body mass index as a prognostic marker for biochemical recurrence in Dutch men treated with radical prostatectomy

> Body mass index is not a predictor of biochemical recurrence after radical prostatectomy in Dutch men diagnosed with prostate cancer

> Blood lipid levels and prostate cancer risk; a cohort study

> Risk of prostate cancer among cancer survivors in the Netherlands