miR-1 and miR-133b are differentially expressed in patients with recurrent prostate cancer

Abstract

Prostate cancer (PCa) is currently the most frequently diagnosed malignancy in the western countries. It is more prevalent in older men with 75% of the incident cases above 65 years old. After radical prostatectomy, approximately 30% of men develop clinical recurrence with elevated serum prostate-specific antigen levels. Therefore, it is important to unravel the molecular mechanisms underlying PCa progression to develop novel diagnostic/therapeutic approaches. In this study, it is aimed to compare the microRNA (miRNA) profile of recurrent and non-recurrent prostate tumor tissues to explore the possible involvement of miRNAs in PCa progression. Total RNA from 41 recurrent and 41 non-recurrent PCa tissue samples were used to investigate the miRNA signature in PCa specimens. First of all, 20 recurrent and 20 non-recurrent PCa samples were profiled using miRNA microarray chips. Of the differentially expressed miRNAs, miR-1, miR-133b and miR-145* were selected for further validation with qRT-PCR in a different set of 21 recurrent and 21 non-recurrent PCa samples. Data were statistically analyzed using two-sided Student's t-test, Pearson Correlation test, Receiver operating characteristic analysis. Our results demonstrated that miR-1 and mir-133b have been significantly downregulated in recurrent PCa specimens in comparison to non-recurrent PCa samples and have sufficient power to distinguish recurrent specimens from non-recurrent ones on their own. Here, we report that the relative expression of miR-1 and mir-133b have been significantly reduced in recurrent PCa specimens in comparison to non-recurrent PCa samples, which can serve as novel biomarkers for prediction of PCa progression.

Figure 1. Heatmap representation of significantly deregulated miRNAs.

(A) Heat-map representation of significantly deregulated miRNAs in recurrent PCa specimens vs. non-recurrent PCa specimens. (B) Heat-map representation of miR-1, miR-133b and miR-145* in recurrent PCa specimens vs. non-recurrent PCa specimens.

Figure 2. Relative expression levels of miR-1, miR-133b, and miR-145*.

Relative expression levels of (A) miR-1, (B) miR-133b, and (C) miR-145* in 20 recurrent PCa specimens compared to 20 non-recurrent PCa specimens. RNU43 was used for normalization of miRNA expression analyses.

Figure 3. Pearson Correlation analysis of miR-1 and miR-133b.

Figure 4. ROC analysis of miR-1 and miR-133b.

Curves for individual miRNAs and their cooperative power to discriminate two sets of patients comprised of 20 recurrent and 20 non-recurrent PCa specimens.