Diagnostic, prognostic and predictive value of cell-free miRNAs in prostate cancer: a systematic review

Abstract

Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing substantially improved early detection of prostate cancer, however it also led to overdiagnosis and subsequent overtreatment of patients with an indolent disease. Treatment outcome and management of prostate cancer could be improved by the development of non-invasive biomarker assays that aid in increasing the sensitivity and specificity of prostate cancer screening, help to distinguish aggressive from indolent disease and guide therapeutic decisions. Prostate cancer cells release miRNAs into the bloodstream, where they exist incorporated into ribonucleoprotein complexes or extracellular vesicles. Later, cell-free miRNAs have been found in various other biofluids. The initial RNA sequencing studies suggested that most of the circulating cell-free miRNAs in healthy individuals are derived from blood cells, while specific disease-associated miRNA signatures may appear in the circulation of patients affected with various diseases, including cancer. This raised a hope that cell-free miRNAs may serve as non-invasive biomarkers for prostate cancer. Indeed, a number of cell-free miRNAs that potentially may serve as diagnostic, prognostic or predictive biomarkers have been discovered in blood or other biofluids of prostate cancer patients and need to be validated in appropriately designed longitudinal studies and clinical trials. In this review, we systematically summarise studies investigating cell-free miRNAs in biofluids of prostate cancer patients and discuss the utility of the identified biomarkers in various clinical scenarios. Furthermore, we discuss the possible mechanisms of miRNA release into biofluids and outline the biological questions and technical challenges that have arisen from these studies.

The putative tumour suppressor miR-1-3p modulates prostate cancer cell aggressiveness by repressing E2F5 and PFTK1

“…Multiple miRNAs have been observed to be involved in several crucial processes in PCa, such as cell proliferation, apoptosis, invasion and metastasis [9, 12, 14, 15, 17]. The tumor suppression activity of miR-1-3p during tumorigenesis has been well-characterized in several cancers, including colorectal cancer [20], bladder cancer [22] and prostate cancer [18, 19].…”

Comparison of miRNA and gene expression profiles between metastatic and primary prostate cancer

“…miRNAs have been demonstrated to serve important roles in a number of cellular processes as post-transcriptional regulators, in addition to roles in cancer development and progression (5,6). Dysregulation of miRNAs has been demonstrated to contribute to tumorigenesis by stimulating proliferation, angiogenesis and invasion (7,8).…”

Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer

“…For example, Brase et al screened more 60 exosomal miRNAs identifying mir-375 and mir-141 as appropriate markers for prostate cancer [54]. This miRNAs content in exosomes could be considered as a potential novel biomarker for prostate cancer that may be used to diagnose but also to predict the disease stage [55,56]. This is currently needed because the blood level of the gold standard marker for prostate cancer, PSA, do not always correlate with disease stage and aggressiveness of the malignancy [57].…”