The clinical utility of plasma microRNA biomarkers for the detection of aggressive prostate cancer

F Matin1,2, L Moya1,2, V Jeet1,2, J Clements1,2 and J Batra1,2

  1. Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia
  2. Australian Prostate Cancer Research Centre Queensland, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Australia

One of the most pressing challenges today is the search for accurate biomarkers to stratify the risk of aggressive prostate cancer (PCa) at the time of diagnosis. miRNAs, a class of ~22 nucleotide non-coding RNAs regulating gene expression post-transcriptionally, have provided a viable option. Our study aims to identify miRNA biomarkers in plasma, delineate their functional attributes in PCa pathogenesis, and determine putative miRNA targets. Plasma samples were collected from 42 PCa patients with ≤5 years (n=12) and >5 years (n=30) survival from the time of PCa diagnosis, and 19 healthy controls. We screened 372 cancer-associated miRNAs in pooled samples using miScript PCR arrays and validated the shortlisted 35 miRNAs. We further determined in vitro, by introducing miRNA mimics, the effect of selected miRNAs on the proliferation of PCa cell lines. Selection and validation of 35 differentially expressed miRNAs led to the identification of 13 miRNAs (p<0.05) capable of predicting aggressive disease. Preliminary functional analysis of some of these miRNAs revealed that one miRNA decreased proliferation in PC3 cells, whereas, another increased proliferation in LNCaP cells. Further validation of the functional role of the shortlisted miRNAs is in progress and will be followed by the identification of miRNA target genes. Our study will establish whether the assessment of distinct miRNA expression levels can be a better PCa prognosis biomarker. Furthermore, characterisation of the functional roles and identification of miRNA targets may pave the way for the development of novel therapeutic modalities.