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Microbiomes of Urine and the Prostate Are Linked to Human Prostate Cancer Risk Groups

 

New paper published today titled "Microbiomes of Urine and the Prostate Are Linked to Human Prostate Cancer Risk Groups" in European Urology Oncology. 

Papers are coming like buses this week. Delighted that after nine years of work our paper looking at the link between bacteria and aggressive prostate cancer is out. This is exciting stuff.

https://doi.org/10.1016/j.euo.2022.03.006

We already know of some strong associations between infections and cancer. For example, the presence of Helicobacter pylori bacteria in the digestive tract can lead to stomach ulcers and is associated with stomach cancer, and some types of the HPV virus can cause cervical cancer. We wanted to find out whether bacteria could be linked to the way prostate cancer grows and spreads.

We analysed urine or tissue samples from more than 600 patients with or without prostate cancer. And we developed methods of finding the bacteria associated with aggressive prostate cancer. We found several types of bacteria associated with aggressive prostate cancer, some of which are new types of bacteria never found before. The set of bacteria found include Anaerococcus, Peptoniphilus, Porphyromonas, Fenollaria and Fusobacterium. All of these are anaerobic, which means they like to grow without oxygen present.



When any of these specific anaerobic bacteria were detected in the patient’s samples, it was linked to the presence of higher grades of prostate cancer and more rapid progression to aggressive disease. We also identified potential biological mechanisms of how these bacteria may be linked to cancer. Among the things we don’t yet know is how people pick up these bacteria, whether they are causing the cancer, or whether a poor immune response permits the growth of the bacteria. But we hope that our findings and future work could lead to new treatment options, that could slow or prevent aggressive prostate cancer from developing. Our work could also lay the foundations for new tests that use bacteria to predict the most effective treatment for each man’s cancer.


Amazing collaboration between Norwich Medical School UEA, Quadram Institute, the NNUH and others. It was funded by the by Prostate Cancer UK and The Bob Champion Cancer Trust.

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Integration of Urinary EN2 Protein & Cell-Free RNA Data in the Development of a Multivariable Risk Model for the Detection of Prostate Cancer Prior to Biopsy

New paper published today titled "Integration of Urinary EN2 Protein & Cell-Free RNA Data in the Development of a Multivariable Risk Model for the Detection of Prostate Cancer Prior to Biopsy" in "Cancers". In this paper we look at combining two different types of measurements taken from different parts of urine, to see if they can help us better detect prostate cancer and determine how agressive it is. Prostate cancer is a disease responsible for a large proportion of all male cancer deaths but there is a high chance that a patient will die with the disease rather than from. Therefore, there is a desperate need for improvements in diagnosing and predicting outcomes for prostate cancer patients to minimise overdiagnosis and overtreatment whilst appropriately treating men with aggressive disease,  especially if this can be done without taking an invasive biopsy. In this work we develop a test that predicts whether a patient has prostate cancer and how aggressive the disease is from a urine sample. This model combines the measurement of a protein-marker called EN2 and the levels of 10 genes measured in urine. And proves that integration of information from multiple, non-invasive biomarker sources has the potential to greatly improve how patients with a clinical suspicion of prostate cancer are risk-assessed prior to an invasive biopsy.

https://doi.org/10.3390/cancers13092102

It was funded by the by Movember Foundation GAP1 Urine Biomarker project, The Masonic Charitable Foundation, The Bob Champion Cancer Trust, the King family, The Andy Ripley Memorial Fund and the Stephen Hargrave Trust. Further urine biomarker work funded by Prostate Cancer UK
 and the Tesco Centenary Grant. With great work from Shea Connel as first author.

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A novel stratification framework for predicting outcome in patients with prostate cancer

In all the madness I forgot to post about our latest publication published last Friday: A novel stratification framework for predicting outcome in patients with prostate cancer. Found in the British Journal of Cancer. 

We have discovered why some prostate cancers are more aggressive, spread to different parts of the body, and ultimately cause death.

Recently we developed a test to distinguish aggressive prostate cancers from less threatening forms of the disease, by applying some complex maths known as Latent Process Decomposition, that will help avoid sometimes-damaging unnecessary treatment. This aggressive form of prostate cancer is known as DESNT - which has the worst clinical outcomes for patients. In this study we carry on this work and studied gene expression levels in 1,785 prostate cancer tumour samples.

We show how the number of ‘aggressive’ cells in a tumour sample defines how quickly the disease will progress and spread. The more DESNT cells, the quicker the patient is likely to progress. We also revealed three new subtypes of prostate cancer that could be used to stratify patients for different treatments.

The research was funded by the Bob Champion Cancer Trust, the Masonic Charitable Foundation, the King Family, the Hargrave Foundation, and UEA, with support from Movember, Prostate Cancer UK, Callum Barton and from the Andy Ripley Memorial Fund.

https://doi.org/10.1038/s41416-020-0799-5

Kudos link: https://www.growkudos.com/publications/10.1038%25252Fs41416-020-0799-5/reader


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Development of a multivariable risk model integrating urinary cell DNA methylation & cell-free RNA data for the detection of significant prostate cancer

New paper out today in "The Prostate"

"Development of a multivariable risk model integrating urinary cell DNA methylation & cell-free RNA data for the detection of significant prostate cancer"

This carries on from the work last year on a urine test called ‘PUR’ (Prostate Urine Risk) which diagnoses aggressive prostate cancer and predicts whether patients will require treatment up to five years earlier than standard clinical methods.

This latest research combines information from two different levels of biological data in urine (methylation and gene expression) and shows the possibilities of further improves in a urine tests use for diagnosis.

What I really like about this one is the robust machine learning techniques we've used and the alignment to the TRIPOD guidelines.

Great work led by my PhD student Shea O'Connell.

Funded mainly by Movember and The Andy Ripley Memorial Fund.

https://doi.org/10.1002/pros.23968

Press:
Urine test could help reduce unnecessary prostate cancer biopsies
Outlet: MailOnline Date: 10/03/2020 00:08
Click to open
Unnecessary prostate cancer biopsies could be reduced by 60 per cent thanks to new research from the University of East Anglia. Lead author Shea Connell and senior author Dr Dan Brewer (both MED) quoted.
AND
I'm still alive thanks to the quick thinking of my mate Sir Tom
Outlet: Daily Express, p.21 Date: 10/03/2020 00:00
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Progress on urine test for prostate cancer
Outlet: The Guardian, p.16 Date: 10/03/2020 00:00
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Urine test could help reduce unnecessary prostate cancer biopsies
Outlet: ITV (Online) Date: 10/03/2020 11:08
Click to open
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UEA scientists in prostate cancer breakthrough
Outlet: Eastern Daily Press (EDP), p.22 Date: 19/03/2020 00:00
+ 198 more


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The landscape of viral associations in human cancers

A new paper from the PCAWG pathogens group (that we are a part of) is out today in Nature Genetics: 'The landscape of viral associations in human cancers'. Plenty of really interesting insights in there. We discovered traces of 23 different virus types in 356 cancer patients, with 13 percent of the samples having evidence of the presence of viruses. When analysing the whole cancer genome, we discovered traces of viruses in considerably more tumours than in earlier studies that were based on investigating the RNA only. We also further identified some of the mechanisms that viruses use to trigger changes in the DNA of cancer cells. This is the first time that a systematic study of the majority of cancer types for viruses has been made. It is important as unveiling new links between infection and cancer types has the potential to provide actionable opportunities, for example HPV vaccines, which could reduce the global impact of cancer. This is part of the PanCancer suite of papers.

Finally, here is a layman's article that I wrote for The Conversation.


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A four‐group urine risk classifier for predicting outcomes in patients with prostate cancer.

Really pleased to announce the publication of our latest bit of research

https://doi.org/10.1111/bju.14811


We have developed a urine test to diagnose aggressive prostate cancer and predict whether patients will require treatment up to five years earlier than standard clinical methods. The experimental new test called ‘PUR’ (Prostate Urine Risk) also identifies men who are up to eight times less likely to need treatment within five years of diagnosis. It is hoped that the breakthrough could help large numbers of men avoid an unnecessary initial biopsy and repeated invasive follow-ups for ‘low risk’ patients on active surveillance.

This work was funded by the Movember Foundation, The Masonic Charitable Foundation, The Bob Champion Cancer Trust, the King family, the Andy Ripley Memorial Fund and the Stephen Hargrave Trust.

We've had quite a bit of press attention:

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The LPD paper, the research that got some publicity last week, is finally up at the publishers website.

The LPD paper, the research that got some publicity last week, is finally up at the publishers website. http://dx.doi.org/10.1016/j.euf.2017.01.016
http://dx.doi.org/10.1016/j.euf.2017.01.016

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