Abstract
Due to heterogeneous multifocal nature of prostate cancer (PCa), there is currently a lack of biomarkers that stably distinguish it from benign prostatic hyperplasia (BPH), predict clinical outcome and guide the choice of optimal treatment. In this study RNA-seq analysis was applied to formalin-fixed paraffin-embedded (FFPE) tumor and matched normal tissue samples collected from Russian patients with PCa and BPH. We identified 3384 genes differentially expressed (DE) (FDR < 0.05) between tumor tissue of PCa patients and adjacent normal tissue as well as both tissue types from BPH patients. Overexpression of four of the discovered genes (ANKRD34B, NEK5, KCNG3, and PTPRT) was validated by RT-qPCR. Furthermore, the enrichment analysis of overrepresented microRNA and transcription factor (TF) recognition sites within DE genes revealed common regulatory elements of which 13 microRNAs and 53 TFs were thus linked to PCa for the first time. Moreover, 8 of these TFs (FOXJ2, GATA6, NFE2L1, NFIL3, PRRX2, TEF, EBF2 and ZBTB18) were found to be differentially expressed in this study making them not only candidate biomarkers of prostate cancer but also potential therapeutic targets.
Highlights
Prostate cancer (PCa) is the most commonly diagnosed and third-leading cause of cancer-related death among men in developed countries [1]
We identified 3384 genes differentially expressed (DE) (FDR < 0.05) between tumor tissue of prostate cancer (PCa) patients and adjacent normal tissue as well as both tissue types from benign prostatic hyperplasia (BPH) patients
The RNA sequencing (RNA-Seq) analysis of RNA samples isolated from thin paraffin sections of prostate tissue provided the expression profiles reflecting the substantial part of the transcriptional activity of this tissue
Summary
Prostate cancer (PCa) is the most commonly diagnosed and third-leading cause of cancer-related death among men in developed countries [1]. Such highly prevalent malignancy is obviously subjected to numerous studies including those aimed at finding its specific biomarkers. The perspective way of searching for such biomarkers is to conduct the analysis of gene expression in prostate tissue by means of RNA sequencing (RNA-Seq).
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