title: Novel RNA biomarkers of prostate cancer revealed by RNA-seq analysis of formalin-fixed samples obtained from Russian patients.
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.
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia.|Moscow Institute of Physics and Technology, Dolgoprudnyi, Russia.
authors.forename: Anastasia S
authors.initials: AS
authors.lastname: Nikitina
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Sharova
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia.
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Danilenko
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia.
authors.forename: Tatiana B
authors.initials: TB
authors.lastname: Butusova
authors.affiliation: Department of Urology, Moscow State Medical Stomatological University, Moscow, Russia.
authors.forename: Alexandr O
authors.initials: AO
authors.lastname: Vasiliev
authors.affiliation: Department of Urology, Moscow State Medical Stomatological University, Moscow, Russia.
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Govorov
authors.affiliation: Department of Urology, Moscow State Medical Stomatological University, Moscow, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Prilepskaya
authors.affiliation: Department of Urology, Moscow State Medical Stomatological University, Moscow, Russia.
authors.forename: Dmitry Y
authors.initials: DY
authors.lastname: Pushkar
authors.affiliation: Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia.|Moscow Institute of Physics and Technology, Dolgoprudnyi, Russia.
authors.forename: Elena S
authors.initials: ES
authors.lastname: Kostryukova
mesh_terms: D000368:Aged; D005557:Formaldehyde; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012426:Russia; D017423:Sequence Analysis, RNA / Q000379:methods*; D016707:Tissue Fixation; D014157:Transcription Factors / Q000235:genetics
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs; D014157:Transcription Factors; D005557:Formaldehyde
keywords: FFPE; RNA biomarkers; RNA-Seq; benign prostatic hyperplasia; prostate cancer