Study leads way to early detection and treatment of aggressive prostate cancer

TRI-based researchers from QUT have taken a major step towards improving
the current diagnostic test to help distinguish aggressive from non-aggressive prostate cancers.

They have uncovered functionality of a particular prostate cancer genetic variation – or single nucleotide polymorphism (SNP) - in the prostate specific antigen gene.

The findings may help determine the level of treatment a patient needs, such as identifying high-risk men needing early treatment, while saving others from unnecessarily undergoing painful procedures.

The work was a multi-national collaborative effort with more than 60 co-authors and has been published in Nature Communications.

TRI Preclinical Imaging Facility contributed to the huge body of research data, with optical imaging (bioluminescence), ultrasound, X-ray, and microCT imaging techniques used in preclinical studies.

•     Nature Communications article reveals the functionality of the germline mutation – SNP – in the prostate specific antigen – PSA
•     The current PSA test cannot distinguish between non-aggressive and aggressive, deadly prostate cancer
•     Multinational team has uncovered in tests that the SNP is associated with both reduced prostate cancer risk and an aggressive type of this cancer
•     These insights will help develop point-of-care prognostics and improved treatments.

First author on the publication, TRI-based Dr Srilakshmi Srinivasan from QUT’s School of Biomedical Sciences, said the researchers studied the role of a particular prostate cancer genetic variation – or SNP.

“Through comprehensive lab and preclinical tests we found that this SNP, although associated with reduced prostate cancer risk, is also associated with an aggressive type of this cancer,” Dr Srinivasan said.

“This SNP contributes to reduced serum prostate-specific antigen (PSA) levels that may lead to detection bias during PSA screening leading to delayed diagnosis and treatment.”

Dr Srinivasan said the findings gave some insight into anomalies associated with current diagnostics and treatments for what is the second most common cancer in men world-wide.

“The PSA test has long been used as the basis of non-invasive diagnostic and prognostic prostate cancer tests, and it has saved lives,” she said.

“However, the PSA test cannot identify aggressive versus non-aggressive types of cancer which means some tumours with high PSA in the blood can lead to over-diagnoses with over-treatment.

“This means often men undergo painful procedures such as biopsies for accurate diagnoses which affects their quality of life and incurs extra health system costs.

“Furthermore, because the SNP affects the serum PSA levels, tumours which exhibit low levels of PSA in the blood can get missed during early screening, leading to highly aggressive disease with high mortality."

Professor Jyotsna Batra, who led the study, said the research team was now using the information that men with genetic variations in the gene which codes for PSA could be predisposed to aggressive prostate cancer to develop tools that could be used by GPs to identify high-risk patients, but with low blood PSA levels.

“Findings from this study may lead to developing a novel and simple point-of-care device,” Professor Batra said.

“It is an important step forward in an era of personalised medicine because it can provide an individualised diagnostic assessment that can be a guide for more appropriate clinical care.”

QUT Distinguished Professor Emeritus Judith Clements, who co-led the research, said: “Our findings might enable better prognostic prediction and, by distinguishing the more aggressive cancers, identify a high-risk group that needs early treatment.”

This project is part of Professor Batra’s research focus on unravelling the genetic intricacies of hereditary disorders using bioinformatics and experimental approaches.

The QUT team comprises Professor Batra, Dr Srinivasan, Dr Achala Fernando, Emeritus Distinguished Professor Clements, Associate Professor Nathalie Bock, Adjunct Professor Ian Vela, Adjunct Professor Rupert C Ecker and Adjunct Professor Nigel Brown. TRI Preclinical Imaging Facility contributors include Senior Preclinical Imaging Scientist Dr Brian Tse and Preclinical Imaging Officer Dr Kamil Sokolowski, alongside TRI Scientific Services Officer Carson Stephens and TRI-based Dr Thomas Kryza from AdvanCell.

The published paper:

Srinivasan S, Kryza T, Bock N. et al. A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer. Nat Commun 15, 9587 (2024). DOI: doi.org/10.1038/s41467-024-52472-6