MiRNA biomarkers in cancers of the male reproductive system: Are we approaching clinical application?

Abstract

Background: Specific cancer types face specific clinical management challenges.Owing to their stability, robustness and fast, easy and cost-effective detection, microRNAs (miRNAs) are attractive candidate biomarkers to the clinic.Objectives: Based on a comprehensive review of the relevant literature in the field, we explore the potential of miRNAs as biomarkers to answer relevant clinical dilemmas inherent to cancers of the male reproductive tract (prostate [PCa], testis [TGCTs] and penis [PeCa]) and identify some of the challenges/limitations hampering their widely application. Results and discussion:We conclude that the use of miRNAs as biomarkers is at different stages for these distinct cancer types. While for TGCTs, miRNA-371a-3p is universally accepted to fill in important clinicals gaps and is moving fast towards clinical implementation, for PCa almost no overlap of miRNAs exists between studies, denoting the absence of a consistent miRNA biomarker, and for PeCa the field of miRNAs has just recently started, with only a few studies attempting to explore their clinical usefulness. Conclusion:Technological advances influencing miRNA detection and quantification will be instrumental to continue to move forward with implementation of miRNAs in the clinic as biomarkers for non-invasive diagnosis, risk stratification, treatment monitoring and follow-up.

Evolution of Testicular Germ Cell Tumors in the Molecular Era With Histogenetic Implications

“…[58][59][60] One of the major drawbacks is that teratoma secretes low levels of circulating miRNA and cannot provide clinical utility. 61,62 Hemolysis may affect the measurements, which demands refinement in the laboratory techniques. In addition, laboratory quality controls and proper validations are required to implement this assay for clinical utilization.…”

“…In the liquid biopsy studies, miR-371–373 showed better sensitivity than serum biomarkers ie, AFP, HCG, and LDH to detect postchemotherapy residual disease and recurrence 58–60 . One of the major drawbacks is that teratoma secretes low levels of circulating miRNA and cannot provide clinical utility 61,62 …”

MicroRNAs for detecting occult genitourinary cancer

“…MiR-371a-3p is part of a cluster located at chromosome 19, which includes 3 miRNAs: miR-371a-3p, mir-372-3p and miR-373-3p [20][21][22]. The cluster's members are specifically expressed in human embryonic stem cells (ESCs) and have been widely studied as potential TGCT biomarkers, being first suggested in 2011 [21,23]. The most promising miRNA of the three is miR-371a-3p.…”

Small RNAs in andrology: Small messengers with large perspectives

“…In this special issue, we learn more about how miR‐371a‐3p may be used in clinical diagnosis, 13 and how useful it is to predict whether a germ cell tumor is still present after retroperitoneal lymph node dissection in patients with pure seminoma 14 . Finally, we learn how miR‐515‐5p is modulated by a long non‐coding RNA in prostate cancer, 15 and we get an overview on the status of miRNA‐based biomarkers among urological cancers 16 . Outside an oncological setting, we also learn about the sncRNA profiles in the seminal plasma of men with azoospermia and poor semen quality 17–19 …”

“…14 Finally, we learn how miR-515-5p is modulated by a long non-coding RNA in prostate cancer, 15 and we get an overview on the status of miRNA-based biomarkers among urological cancers. 16 Outside an oncological setting, we also learn about the sncRNA profiles in the seminal plasma of men with azoospermia and poor semen quality. [17][18][19] Several miRNAs have also been considered as therapeutic targets, and the number of clinical trials, including the administration of specific miRNAs or anti-miRNAs, is growing.…”