A microRNA molecular signature of aggressive prostate cancer

To date, prostate cancer (PCa) remains a medical challenge, being one of the most prevalent causes of cancer deaths in men worldwide (1). A major innovation in the management of PCa was demonstrated by the measurement of prostate specific antigen (PSA) in the serum of PCa patients in the mid-1980s; however, it is well known that measurement of PSA levels is associated with over-diagnosis and over-treatment. Although over-treatment may be reduced by improved risk stratification where very low or low risk PCa can be monitored by active surveillance and intermediate or high risk PCa can be subjected to treatment, many urologists and patients are reluctant to delay treatment due to the absence of a reliable indicator of aggressive disease and thus, there is a possibility of missing treatment of aggressive PCa patients (2,3). A single threshold PSA test is unable to distinguish between high and low risk PCa (4), and prostate biopsy is often unreliable for the prediction of cancer grade, as only a small fraction of the prostate is sampled during a biopsy for staging (5). Several promising blood based and urinary biomarkers such as the prostate health index (PHI), 4K score and PCA3 for tumour aggressiveness have been identified and recommended to reduce the number of unnecessary biopsies in PSA tested men (6,7). However, in order to appreciate the clinical value of these biomarkers, additional unbiased prospective studies are still required. It is anticipated that the availability of unique molecular signatures and novel biomarkers would lead to an improvement in the management of patients with aggressive PCa, and microRNAs (miRNAs) are pioneers in this area.