Introduction

Prostate cancer [PCa] is a heterogeneous disease, ranging from small, indolent, low-grade tumours, to large, aggressive, life-threatening tumours. It is one of the common malignant tumours and is the third-leading cause of cancer-related deaths in the world. According to WHOs’ projections for 2040, the number of deaths caused by PCa is expected to nearly double, while the number of newly diagnosed cases could reach 2,300,000 per year worldwide.1 The occurrence of Prostate cancer differs substantially by race, ethnicity, and geography; these disparities may be attributed to differences in exposure to risk factors, access to screening and treatment and underlying biology of prostate carcinogenesis.2 With the rising population, better average life expectancy, the epidemiological future predictions do not look promising.3

The patient care and outcome is fundamentally impacted by the diagnosis of prostate cancer and appropriate staging. Traditionally, a digital rectal examination (DRE) and a prostate-specific antigen (PSA) blood test have been used to identify prostate cancer (PCa). This is followed by a transrectal ultrasound (TRUS) guided biopsy.4 After the introduction of the prostate-specific antigen (PSA) screening test, the detection of PCa has dramatically increased with a peak in the early 1990s.5 Despite the significant improvement in early detection due to routine PSA testing, there are debates about its benefits because there is no consensus regarding whether it effectively reduces the risk of death from the disease. This is due to the fact that serum PSA levels are prostate but not cancer specific and fluctuate due to, for example, infections, inflammation, or benign prostatic hyperplasia (BPH), resulting in high false-positive rates. The poor correlation between PSA levels and disease state leads to unnecessary diagnoses and overtreatment of indolent PCa.6

With an ageing population, the number of prostate cancer cases will increase dramatically in the next few decades and represents a substantial public health burden. Although clinical parameters such as prostate specific antigen (PSA) value, imaging diagnostics and histopathological scores (e.g. Gleason score) allow certain risk stratification, they do not allow a definite statement about the individual patient’s prognosis. This might lead to unnecessary treatment on the one hand, but also deny potentially favourable treatment on the other hand, and ultimately harm the patient. Consequently the current tendencies in the treatment course of patients with PCa increase the need for reliable biomarkers that help in decision-making in a challenging clinical setting.7

Henceforth beyond proteins and messenger RNAs (mRNAs), which have shown clinical utility in various clinical scenarios, there is a growing interest in the potential utility of microRNAs as PCa biomarkers. Around 2008, three independent studies demonstrated that tumour-associated miRNAs are released into the blood circulation and are present in human plasma and serum in a remarkably stable form.8 More recently, cell free miRNAs have also been found in a variety of other biofluids.9 Given that miRNA expression patterns are tissue and cancer-type specific, these findings led to the concept that different cancers may leave specific miRNA signatures in biofluids,10 and that these signatures may carry information about the disease status, aggressiveness and response to therapy.

The miRNAs are evolutionarily conserved short (approximately 18–22 nucleotides) non-coding single-stranded RNA molecules that act as posttranscriptional gene regulators. The miRNAs are attractive molecular biomarker candidates because they can be reproducibly extracted from a wide range of biologic samples, do not require invasive biopsies and are generally stable and resistant to various storage conditions.11 Importantly, miRNAs can be easily detected and accurately quantified by a variety of widely used standard techniques, such as qRT-PCR, microarray, and small RNA sequencing. The stability, lower structure complexity, and lack of modifications make circulating miRNAs to be ideal diagnostic biomarkers.

Following the initial discovery by Mitchell et al.12 providing a proof of principle that miRNAs from prostate cancer cells are released in the bloodstream, where they are readily detectable by PCR-based methods, studies have explored miRNAs in biofluids and prostate tissue of prostate cancer patients. A summary of the known miRNAs associated with Prostate cancer is given in the Table 1.

Future Perspective

With a growing surge of research on miRNA as potential biomarkers in PCa, some questions are being answered, while many new ones are being asked. There is still no clear vision whether there is a distinct future for miRNA translation into clinical practice. On that account, additional research on all aspects of miRNA analysis right from preanalytics to clinical correlation in multiple, large cohorts may ensure an unambiguous conclusion.

Although there is still much work to be done before non-invasive miRNA biomarkers can begin to be used in the clinical setting, it is beyond doubt that miRNAs hold a significant promise as a potential non-invasive biomarker, creating a way for an individual patient-centred oncological approach in the near future.14

Conflict of Interest

None.