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.

NEK5 promotes breast cancer cell proliferation through up‐regulation of Cyclin A2

“…In terms of NEK5 mRNA expression, our observation was fully congruent with the observation made by Nikitina et al in prostate cancer that NEK5 mRNA was displayed to be remarkably higher in cancer tissues relative to normal controls. Regrettably, there has been short of data regarding the biological roles of NEK5 in the study by Nikitina et al Here, we report that NEK5 was an independent prognostic predictor in breast cancer in addition to the significant correlation with tumor size, TNM stage and Ki‐67 status.…”

“…There having been a paucity of clinical data regarding NEK5 in the context of cancer till now, except for one recent study by Nikitina et al reporting that NEK5 mRNA was found to be over‐expressed in prostate cancer tissues relative to paired normal control tissues from Russian. To understand the NEK5 expression in breast cancer tissues, we performed immunohistochemistry (IHC) on breast cancer tissue microarray consisting of 203 paired cases of breast cancer and its matched normal controls.…”

“…The role NEK5 mediated in cancer was still yet poorly understood, although implication of NEK5 in the regulation of centrosome integrity and mitotic spindle assembly has been elaborately reviewed. Nikitina et al firstly discovered that NEK5 mRNA was drastically up‐regulated in prostate cancer using RNA sequencing in samples from Russians. Inspired by the study together with its elusive function in cancer, we were therefore determined to go on to follow‐up the NEK5 in breast cancer, which was why we picked up NEK5 herein.…”

Multiple roles and regulatory mechanisms of the transcription factor GATA6 in human cancers

“…In a study of animal models of sebaceous gland (SG) tumors, Gata6 was found to control sebaceous gland development and cancer . Because GATA6 can be differentially expressed in prostate cancer, GATA6 can be used not only as a candidate biomarker for prostate cancer, but also as a potential therapeutic target . The transcription factor GATA6 is also associated with the occurrence of adrenocortical tumors .…”

“…102 Because GATA6 can be differentially expressed in prostate cancer, GATA6 can be used not only as a candidate biomarker for prostate cancer, but also as a potential therapeutic target. 103 The transcription factor GATA6 is also associated with the occurrence of adrenocortical tumors. 104,105 As shown in Table 1, the link between the transcription factor GATA6 and other cancers has been summarized.…”