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. 2017 May 16;8(20):32990-33001.
doi: 10.18632/oncotarget.16518.

Novel RNA biomarkers of prostate cancer revealed by RNA-seq analysis of formalin-fixed samples obtained from Russian patients

Anastasia S Nikitina  1   2 , Elena I Sharova  1 , Svetlana A Danilenko  1 , Tatiana B Butusova  1 , Alexandr O Vasiliev  3 , Alexandr V Govorov  3 , Elena A Prilepskaya  3 , Dmitry Y Pushkar  3 , Elena S Kostryukova  1   2
Affiliations

Novel RNA biomarkers of prostate cancer revealed by RNA-seq analysis of formalin-fixed samples obtained from Russian patients

Anastasia S Nikitina et al. Oncotarget. .

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.

Keywords: FFPE; RNA biomarkers; RNA-Seq; benign prostatic hyperplasia; prostate cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interests.

Figures

Figure 1
Figure 1. MDS-plot of all sequenced samples
The distance between the dots represents the similarity of corresponding samples’ transcriptional profiles.
Figure 2
Figure 2. MDS-plot of the final sample set
The distance between the dots represents the similarity of corresponding samples’ transcriptional profiles.
Figure 3
Figure 3. Comparison of the results obtained with TCGA data
(A) Scatter-plot showing the direction and value of the expression change of every gene differentially expressed both in Russian sample set (logFC_rus) and in TCGA data (logFC_tcga). (B) Number of all DE genes in each sample set (dark - Russian, light – TCGA) whose expression change satisfies a certain condition.
Figure 4
Figure 4. Box-plots representing relative expression levels of genes NEK5, KCNG3 and PTPRT obtained by RT-qPCR
See this image and copyright information in PMC

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