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Clinical Trial
. 2013 Apr 10;14(4):7757-70.
doi: 10.3390/ijms14047757.

Plasma miRNAs as biomarkers to identify patients with castration-resistant metastatic prostate cancer

Akira Watahiki  1 , Robyn J Macfarlane, Martin E Gleave, Francesco Crea, Yuzhuo Wang, Cheryl D Helgason, Kim N Chi
Affiliations
Clinical Trial

Plasma miRNAs as biomarkers to identify patients with castration-resistant metastatic prostate cancer

Akira Watahiki et al. Int J Mol Sci. .

Abstract

MicroRNAs (miRNAs) have emerged as key regulators of numerous biological processes, and increasing evidence suggests that circulating miRNAs may be useful biomarkers of clinical disease. In this study, we sought to identify plasma miRNAs that differentiate patients with metastatic castration resistant prostate cancer (mCRPC) from those with localized prostate cancer (PCa). Pooled plasma samples from patients with localized PCa or mCRPC (25 per group) were assayed using the Exiqon miRNA qPCR panel, and the differential expression of selected candidates was validated using qRT-PCR. We identified 63 miRNAs upregulated in mCRPC versus localized PCa, while only four were downregulated. Pearson's correlation analysis revealed two highly correlated groups: one consisting of miR-141, miR375 and miR-200c and the other including miR151-3p, miR423-3p, miR-126, miR152 and miR-21. A third group, containing miR-16 and miR-205, showed less correlation. One miRNA from each group (miR-141, miR151-3p and miR-16) was used for logistic regression analysis and proved to increase the sensitivity of the prostate-specific antigen (PSA) test alone. While no miRNA alone differentiated localized PCa and mCRPC, combinations had greater sensitivity and specificity. The expression of these 10 candidates was assayed for association with clinical parameters of disease progression through the cBio portal. Our results demonstrate that plasma levels of selected miRNAs are potential biomarkers to differentiate localized PCa and mCRPC.

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Figures

Figure 1
Figure 1
Quantitative RT-PCR analysis of upregulated and downregulated miRNAs in individual plasma samples from patients with localized (local) prostate cancer (PCa) or metastatic castration-resistant PCa (mCRPC). Quantification cycle (Cq) values were converted to log base amounts based on the cell line reference expression as outlined in the Materials section. Statistical analysis was carried out using the Student’s t-test. * indicates p < 0.05, ** indicates p < 0.01 and *** indicates p < 0.001.
Figure 2
Figure 2
Pearson’s correlation amongst the validated differentially expressed miRNAs. Black dots represent localized PCa, and red dots represent mCRPC.
Figure 3
Figure 3
Principle Component Analysis (PCA) on the ten validated differentially expressed miRNAs. (A) Visual representation of the highly correlated pattern observed in the Pearson’s correlation; (B) PCA using all 10 miRNAs is able to distinguish localized PCa from mCRPC; although (C) PCA using a combination of only miR-141 + miR-151-3p + miR-16 shows a similar ability to separate the two conditions.
Figure 4
Figure 4
Receiver operating characteristic (ROC) curves to assess the utility of selected individual miRNAs compared with the combination or with PSA to differentiate localized PCa from mCRPC. ROC curves for miR-141 (light squares), miR-151-3p (triangle), miR-16 (upside-down triangle), the combination of all three miRs (dark square) and PSA (circle).
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