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.

The SEMA3B gene is located in the 3p21.3 LUCA region, which is frequently affected in different types of cancer. The objective of our study was to expand our knowledge of the SEMA3B gene as a tumor suppressor and the mechanisms of its inactivation. In this study, several experimental approaches were used: tumor growth analyses and apoptosis assays in vitro and in SCID mice, expression and methylation assays and other. With the use of the small cell lung cancer cell line U2020 we confirmed the function of SEMA3B as a tumor suppressor, and showed that the suppression can be realized through the induction of apoptosis and, possibly, associated with the inhibition of angiogenesis. In addition, for the first time, high methylation frequencies have been observed in both intronic (32-39%) and promoter (44-52%) CpG-islands in 38 non-small cell lung carcinomas, including 16 squamous cell carcinomas (SCC) and 22 adenocarcinomas (ADC), and in 83 clear cell renal cell carcinomas (ccRCC). Correlations between the methylation frequencies of the promoter and the intronic CpG-islands of SEMA3B with tumor stage and grade have been revealed for SCC, ADC and ccRCC. The association between the decrease of the SEMA3B mRNA level and hypermethylation of the promoter and the intronic CpG-islands has been estimated in renal primary tumors (P < 0.01). Using qPCR, we observed on the average 10- and 14-fold decrease of the SEMA3B mRNA level in SCC and ADC, respectively, and a 4-fold decrease in ccRCC. The frequency of this effect was high in both lung (92-95%) and renal (84%) tumor samples. Moreover, we showed a clear difference (P < 0.05) of the SEMA3B relative mRNA levels in ADC with and without lymph node metastases. We conclude that aberrant expression and methylation of SEMA3B could be suggested as markers of lung and renal cancer progression.

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.