Abstract

Prostate cancer (PCa) is the second most common diagnosed malignant disease in men worldwide. Although serum PSA test dramatically improved the early diagnosis of PCa, it also led to an overdiagnosis and as a consequence to an overtreatment of patients with an indolent disease. New biomarkers for diagnosis, prediction, and monitoring of the disease are needed. These biomarkers would enable the selection of patients with aggressive or progressive disease and, hence, would contribute to the implementation of individualized therapy of the cancer patient. Since the FDA approval of the long noncoding PCA3 RNA-based urine test for the diagnosis of PCa patients, many new noncoding RNAs (ncRNAs) associated with PCa have been discovered. According to their size and function, ncRNAs can be divided into small and long ncRNAs. NcRNAs are expressed in (tumor) tissue, but many are also found in circulating tumor cells and in all body fluids as protein-bound or incorporated in extracellular vesicles. In these protected forms they are stable and so they can be easily analyzed, even in archival specimens. In this review, the authors will focus on ncRNAs as novel biomarker candidates for PCa diagnosis, prediction, prognosis, and monitoring of therapeutic response and discuss their potential for an implementation into clinical practice.

Highlights

  • Circulating exosomal miRNAs were correlated with miRNAs identified in tissue of ovarian cancer [158, 159] and lung cancer [160]. These results suggest that circulating exosomal miRNAs could potentially be used as diagnostic markers in prostate cancer (PCa) [161]

  • PCa and especially castration-resistant prostate cancer (CRPC) are heterogeneous diseases and, it is not expected that a single biomarker for all stages of the disease will be identified

  • The long ncRNAs (lncRNA) PCA3 has already been successfully translated into clinical setting, especially to predict biopsy outcome of patients with elevated serum prostate-specific antigen (PSA)

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Summary

Introduction

The heterogeneous nature of PCa and CRPC is coupled with genetic and epigenetic alterations that occur during disease progression and response to therapy These changes can lead to the expression or production of novel disease-specific macromolecules, which could serve as novel biomarkers. Many excellent reviews have summarized novel candidate biomarkers including proteins (e.g., α-methylacylCoA racemase, endoglin, prostate-specific membrane antigen [PSMA], caveolin-1, interleukin-6, CD147, TGF-β 1, and human kallikrein-2), genetic biomarkers (e.g., TMPRSS2:ETS gene fusions, BRCA1/2 mutations), epigenetic modification (e.g., methylation of the glutathione S-transferase [GSTP1] gene and histone modifications), and expression of (novel) mRNA transcripts in PCa [6, 15,16,17,18,19]. AMACR: α-methylacyl-CoA racemase; CTCs: circulating tumor cells; GSTP1: glutathione S-transferase pi 1; KLK3: kallikrein-3; lncRNAs: long noncoding RNAs; PCa: prostate cancer; PSA: prostate-specific antigen; PSMA: prostate-specific membrane antigen. Further investigations are necessary to confirm these findings, to describe the role of snoRNAs and sdRNAs in (prostate) cancer, and to evaluate their potential as biomarker

What Is Known about Noncoding RNAs in Prostate Cancer?
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