To detect expression of EMT-related genes in prostate tumor samples and analyze a possible correlation between the gene expression level and clinical characteristics of prostate cancer in different groups. Methods. Expression of 19 genes was analyzed in 37 frozen samples of prostate cancer tissues at different tumor stages and Gleason scores, 37 paired conventionally normal prostate tissues and 20 samples of prostate adenomas, using quantitative PCR. Results. We have found that nine genes were expressed differently in benign and malignant prostate tumors, namely AR (isoform 1), AR (isoform 2), PTEN, VIM, MMP9, KRT18, PCA3, HOTAIR and SCHLAP1. When different tumor stages were compared, we could identify six differentially expressed genes: KRT18, MMP9, VIM, PCA3, HOTAIR and SCHLAP1; when samples of tumors with different Gleason score were compared, we found that eight genes were expressed differently: AR (isoform 1), CDH1, KRT18, MMP9, OCLN, PCA3, HOTAIR and SCHLAP1. The datahad a high level of heterogeneity potentially due to various molecular subtypes of prostate cancer, i.e. a luminal subtype with a high expression of CDH1, OCLN, AR(1 isof), KRT18, NKX3-1 and PSA; the stem-like subtype with the high expression of mesenchymal markers CDH2, FN1 and VIM and low expression of the epithelial markers. It is noteworthy that lncRNAs were specifically expressed in these two molecular subtypes. Conclusions. EMT-related genes were differentially expressed in benign and malignant prostate tumors. High heterogeneity of expression levels, especially in adenocarcinoma groups, might suggest the existence of at least two different molecular subtypes, luminal and stem-like. Further experiments are necessary for specification of the molecular subtypes of prostate adenocarcinoma.

A significant need for reliable and accurate cancer diagnostics and prognosis compels the search for novel biomarkers that would be able to discriminate between indolent and aggressive tumors at the early stages of disease. The aim of this work was identification of potential diagnostic biomarkers for characterization of different types of prostate tumors. NotI-microarrays with 180 clones associated with chromosome 3 genes/loci were applied to determine genetic and epigenetic alterations in 33 prostate tumors. For 88 clones, aberrations were detected in more than 10% of tumors. The major types of alterations were DNA methylation and/or deletions. Frequent methylation of the discovered loci was confirmed by bisulfite sequencing on selective sampling of genes: FGF12, GATA2, and LMCD1. Three genes (BHLHE40, BCL6, and ITGA9) were tested for expression level alterations using qPCR, and downregulation associated with hypermethylation was shown in the majority of tumors. Based on these data, we proposed the set of potential biomarkers for detection of prostate cancer and discrimination between prostate tumors with different malignancy and aggressiveness: BHLHE40, FOXP1, LOC285205, ITGA9, CTDSPL, FGF12, LOC440944/SETD5, VHL, CLCN2, OSBPL10/ZNF860, LMCD1, FAM19A4, CAND2, MAP4, KY, and LRRC58. Moreover, we probabilistically estimated putative functional relations between the genes within each set using the network enrichment analysis.

Background: Prostate cancer is one of the most common male cancers in Western countries and takes the third place in morbidity in Ukraine. It is a highly heterogeneous disease. Aim: To analyze relative expression levels of the TGFB1, IL1B, FOS, EFNA5, TAGLN, PLAU, and EPDR1 genes in malignant and non-malignant prostate tissues. Materials and Methods: Total RNA was isolated from 16 prostate adenomas, 37 prostate adenocarcinomas, and 29 conventionally normal prostate tissues. To analyze relative gene expression levels the quantitative real-time polymerase chain reaction was performed. Results: The significant alterations in the relative expression levels were found in all analyzed sample groups for 4 genes: FOS, EFNA5, IL1B, and TGFB1. We have found that FOS and EFNA5 were more frequently overexpressed in carcinomas with Gleason score ≤ 7, compared with adenomas. On contrary, PLAU expression levels were decreased more frequently in prostate cancers, compared with conventionally normal tissues. Noteworthy, we found positive correlation between IL1B expression level and PSA (for patients with slight PSA increase, no more than 20.0 ng/ml). Conclusion: The EFNA5, FOS, IL1B, PLAU, and TGFB1 genes that showed significant expression alterations in prostate tumors, compared with conventionally normal prostate tissue, may play role in prostate cancer development and should be further investigated.

To detect ETS fusion transcripts in Ukrainian population and to analyze a possible relationship between the ETS fusion transcripts and clinical characteristics of prostate cancer. Methods. Quantitative PCR (q-PCR) was used to analyze the expression of six fusion transcripts at the mRNA level. The amplified products were analyzed by gel electrophoresis and direct sequencing. We analyzed 37 fresh frozen samples of prostate cancer tissues, 37 paired conventionally normal prostate tissue samples and 20 samples of adenomas. Results. Six ETS fusion transcripts of TMPRSS2 with ERG, ETV1, ETV4, ETV5 were analyzed. Only one out of six fusion ETS transcripts was detected in a cohort of 37 Ukrainian patients with prostate adenocarcinoma. The frequency of detection of the TMPRSS2-ERG fusion transcript in prostate cancer tissues was 56.8 %. The TMPRSS2-ERG expression was also detected in 16 normal prostate tissue samples (43.2 %) and in 4 prostate adenoma samples (20 %). No correlation was found between the frequency of the TMPRSS2-ERG in carcinoma samples and clinical characteristics of the samples. However, an analysis of relative gene expression in all the investigated groups has shown the altered TMPRSS2-ERG expression in some groups with different Gleason scores of prostate adenocarcinoma compared to adenomas and normal tissue samples. The most elevatedTMPRSS2-ERG expression was found in the prostate adenocarcinoma group with the Gleason score > 7. Conclusions. We detected the TMPRSS2-ERG fusion transcript (EF194202.1) in prostate tumor samples as adenocarcinoma (the frequency was 56.8 %) with different Gleason score andя some paired normal prostate tissues as adenoma samples in our group of Ukrainian population. The obtained results show that the TMPRSS2-ERG fusion transcript is present at early stages of cancer development. In the further studies