Abstract

Prostate cancer is diagnosed in over 1 million men every year globally, yet current diagnostic modalities are inadequate for identification of significant cancer and more reliable early diagnostic biomarkers are necessary for improved clinical management of prostate cancer patients. MicroRNAs (miRNAs) modulate important cellular processes/pathways contributing to cancer and are stably present in body fluids. In this study we profiled 372 cancer-associated miRNAs in plasma collected before (~60% patients) and after/during commencement of treatment (~40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs - miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. The miRNA panel was able to differentiate between prostate cancer patients and controls (AUC = 0.88). Analysis of published miRNA transcriptomic data from clinical samples demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues. Overexpression of miR-152-3p increased proliferation and migration of prostate cancer cells, suggesting a role for this miRNA in prostate cancer pathogenesis, a concept that was supported by pathway analysis of predicted miR-152-3p target genes. In summary, a four miRNA panel, including miR-152-3p which likely targets genes with key roles in prostate cancer pathogenesis, has the potential to improve early prostate cancer diagnosis.

Highlights

  • Prostate biopsy is the gold standard prostate cancer diagnostic tool, it is bound by several limitations[6]

  • We investigated the differential expression of cancer-associated miRNAs in plasma samples collected from age-matched prostate cancer patients and healthy control individuals using miRNA PCR array profiling followed by quantitative real-time PCR

  • Differential expression of miRNAs in pooled plasma samples from prostate cancer patients and healthy controls was measured by quantitative real-time PCR (qRT-PCR) using miScript miRNA PCR arrays, which contained pre-loaded miScript Primer Assays for 372 cancer-associated miRNAs plus 12 internal controls

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Summary

Introduction

Prostate biopsy is the gold standard prostate cancer diagnostic tool, it is bound by several limitations[6]. Considerable research has led to the development of several molecular and genetic assays that have provided a prospective direction for the development of prostate cancer biomarkers[5]. Such assays utilise body fluid- or tissue-based biomarkers for the diagnosis, prognosis and risk stratification of prostate cancer[5]. A number of studies have investigated the diagnostic, prognostic and risk stratification abilities of miRNAs in various diseases[12,13,14], including prostate cancer[15,16,17,18,19], which is summarised in our recently published review[20]. Our study reveals disease-relevant miRNAs with potential to improve the diagnosis of prostate cancer

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