Prostate cancer biomarkers identified in seminal fluid
Improved diagnosis and management of one of the most common cancers in men - prostate cancer - could result from research at the University of Adelaide, which has discovered that seminal fluid (semen) contains biomarkers for the disease.
Results of a study now published in the journal Endocrine-Related Cancer have shown that the presence of certain molecules in seminal fluid indicates not only whether a man has prostate cancer, but also the severity of the cancer.
Speaking in the lead-up to Men’s Health Week (9-15 June), University of Adelaide research fellow and lead author Dr Luke Selth says the commonly used PSA (prostate specific antigen) test is by itself not ideal to test for the cancer.
“While the PSA test is very sensitive, it is not highly specific for prostate cancer,” Dr Selth says. “This results in many unnecessary biopsies of non-malignant disease. More problematically, PSA testing has resulted in substantial over-diagnosis and over-treatment of slow growing, non-lethal prostate cancers that could have been safely left alone.
“Biomarkers that can accurately detect prostate cancer at an early stage and identify aggressive tumors are urgently needed to improve patient care. Identification of such biomarkers is a major focus of our research,” he says.
Dr Selth, a Young Investigator of the Prostate Cancer Foundation (USA), is a member of the Freemasons Foundation Centre for Men’s Health at the University of Adelaide and is based in the University’s Dame Roma Mitchell Cancer Research Laboratories.
Prostate cancer biomarkers identified in seminal fluid" align="right" /> Using samples from 60 men, Dr Selth and colleagues discovered a number of small ribonucleic acid (RNA) molecules called microRNAs in seminal fluid that are known to be increased in prostate tumors. The study showed that some of these microRNAs were surprisingly accurate in detecting cancer.
“The presence of these microRNAs enabled us to more accurately discriminate between patients who had cancer and those who didn’t, compared with a standard PSA test,” Dr Selth says. “We also found that the one specific microRNA, miR-200b, could distinguish between men with low grade and higher grade tumors. This is important because, as a potential prognostic tool, it will help to indicate the urgency and type of treatment required.”
Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.
A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.
Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The purpose of this review is to examine the current status of prostate cancer biomarkers, with special emphasis on emerging markers, by evaluating their diagnostic and prognostic potentials. Both genes and proteins that reveal loss, mutation, or variation in expression between normal prostate and cancerous prostate tissues will be covered in this article. Along with the discovery of prostate cancer biomarkers, we will describe the criteria used when selecting potential biomarkers for further development towards clinical use. In addition, we will address how to appraise and validate candidate markers for prostate cancer and some relevant issues involved in these processes. We will also discuss the new concept of the biomarkers, existing challenges, and perspectives of biomarker development.
This research builds on previous work by Dr Selth’s team, published in the British Journal of Cancer, which demonstrated that microRNAs in the blood can predict men who are likely to relapse after surgical removal of their prostate cancer. “We are excited by the potential clinical application of microRNAs in a range of body fluids,” he says.
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University of Adelaide. “Prostate cancer biomarkers identified in seminal fluid.” ScienceDaily. ScienceDaily, 6 June 2014
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L. A. Selth, M. J. Roberts, C. W. k. Chow, V. R. Marshall, S. A. r. Doi, A. D. Vincent, L. M. Butler, M. F. Lavin, W. D. Tilley, F. Gardiner. Human seminal fluid as a source of prostate cancer specific microRNA biomarkers. Endocrine Related Cancer, 2014; DOI: 10.1530/ERC-14-0234
L A Selth, S L Townley, A G Bert, P D Stricker, P D Sutherland, L G Horvath, G J Goodall, L M Butler, W D Tilley. Circulating microRNAs predict biochemical recurrence in prostate cancer patients. British Journal of Cancer, 2013; 109 (3): 641 DOI: 10.1038/bjc.2013.369