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bacterial correlation and connection, "marker"?

xNTP
Posts: 34
Joined: Oct 2016

I came across this potential bacterial "marker" with other biological aspects, so I'm noting the papers.

B193 Propionibacterium acnes infection of the prostate gland as a risk-factor and biomarker of prostate cancer. 

Andrew McDowell Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Londonderry, United Kingdom.  

Abstract
Prostate cancer (PCa) is the most common male cancer in the UK, killing approximately 11,000 men every year. There is now increasing interest in the role played by the anaerobic bacterium Propionibacterium acnes in the aetiology of this condition via chronic, intracellular and asymptomatic infection of the prostate gland leading to oncogenesis. To investigate this, we developed a novel quantitative real-time PCR assay for retrospective detection of P. acnes in formalin-fixed paraffin-embedded tissue sections prepared from archived prostate biopsy samples. A total of 81 biopsy samples were examined from 53 patients with prostate carcinoma, versus 111 samples from 60 patients whose biopsies were histologically normal. Our assay revealed that 35% of men with PCa were positive for the presence of P. acnes in either one or both prostate lobes compared to only 8% of the normal tissue (Fisher’s exact test, 2-sided; p<0.001). This rate of detection is in keeping with previous culture-based studies, and equates to a 2-fold relative risk (95% CI: 1.45-2.75; p<0.0001) after adjustment for age; this level of risk approximates to having one first-degree relative diagnosed with the condition. No statistical association between the presence or absence of infection/ colonization and age, blood prostate specific antigen (PSA) levels or Gleason score was observed. Our studies suggest P. acnes infection of the prostate gland may be a potential risk factor for PCa development. Furthermore, the presence of P. acnes in cancerous tissue is also a highly specific biomarker for the condition versus PSA measurement (92% versus 65%).

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Propionibacterium acnes induces dysregulation of protease-activated receptor (PAR) gene activity in chronically infected prostate epithelial cells. Andrew McDowell et al, Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Londonderry, United Kingdom. 

Abstract
There is now increasing interest in the role played by the anaerobic bacterium Propionibacterium acnes in the aetiology of prostate cancer (PCa) via chronic, intracellular and asymptomatic infection of the prostate gland leading to oncogenesis. To date, our understanding of how this bacterium could cause PCa remains unclear, although in vitro studies do demonstrate its ability to widely stimulate gene dysregulation and induce cellular transformation of prostate epithelial cells. We have taken a pathway-focused approach to understanding how this bacterium may effect RWPE-1 prostate epithelial cells via dysregulation of protease-activator gene activity (PAR), and associated downstream effectors and target genes. PARs are G-coupled cell surface proteins and are overexpressed in many different cancer types, including PCa where they are associated with tumour growth, invasion, metastasis and biochemical recurrence. Using a PAR signalling gene expression array, our results show that after a chronic 2-week infection in vitro with P. acnes, both PAR-1 and PAR-2 are significantly overexpressed, alongside significant dysregulation of genes encoding potential cancer mediators associated with inflammation, proliferation, angiogenesis and migration. Functional PAR-1 and PAR-2 upregulation was confirmed using a calcium mobilisation assay, which measures an ephemeral rise in intracellular calcium when cells are treated with agonist peptides against the receptors. These results provide additional evidence that P. acnes in the prostate gland may be a clinically relevant observation and a potential risk factor for PCa development.  

Georges Calvez
Posts: 171
Joined: Sep 2018

Hi there,

I would say that is not surprising.
It is already known that the prostate is an organ uniquely susceptible to cancer and that a large number of men that will never develop prostate cancer show the presence of abnormal cells in later life.
The causes of prostate cancer are many, it seems that there are several weak causative factors that can be additive in ways that we do not understand.
There is also the heterogenous nature of the disease, prostate cancer can vary from a benign condition that can be kept underr observation for up to several decades to forms that jump out and colonise everywhere, killing in a few years or less unless aggresively treated.
When we move on from Gleason scoring to taking a complete genetic profile of each new case we will be able to say where any one cancer sits on the band from scratchy kitten to full grown leopard with homicidal intent.

Best wishes,

Georges

VascodaGama's picture
VascodaGama
Posts: 2929
Joined: Nov 2010

xNTP,

Welcome back. I have missed your intriguing and thoughtful entries in this forum. This time you focus on bacteria as a cause in the initiation of prostate cancer. Indeed, the subject is very interesting.

At the beginning of my PCa case, back in 2000, I searched for comprehensive reasons behind the cause of my cancer but didn’t find a study or article on the matter with a conclusive idea on how cancers are initiated. In any case, researchers never gave up and we have today an incredible number of possible alleys leading to that precise answer.

By own experience, I strongly believe that stress caused my case of cancer. We known that tress causes hormonal imbalances in the body, increasing or decreasing the levels of androgen hormones in circulation which lead to temporary suppression of the immune system. This is the timing when bacteria wins and multiplies inducing inflammation that subsequently is attacked by immune cells in a macrophage style.

The researches in your article on the effect of Propionibacterium are quite interesting to me as I read that this bugger was found to cause other diseases in some organs. It seems that it got the ability of escaping detection by the immune sentinels, hiding its presence via a phagocytosis process at the local cells. The pathogenesis process follows which could well lead to genetic and cellular changes transforming healthy cells into cancerous ones.

What made me curious is the idea in creating a preventive measure test (marker as you named it) to use as the substitute of the PSA. Surely such marker would detect issues earlier to any increase of the PSA but nobody could take it to certify cancer. The immune response may well be effective in destroying those cells before these develop into tumours. I wonder what kind of antigen is manufactured that could be associated to the presence of Propionibacterium at the prostate gland.

Nice reading.

Best,

VGama

 

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