Aim: To assess relative expression (RE) levels of CAF-, TAM-specific, immune defense-associated genes in prostate tumors and to show correlation of RE with clinical, pathological and molecular characteristics, with the aim to define clinically significant specific alterations in a gene expression pattern. Methods: RE of 23 genes was analyzed by a quantitative polymerase chain reaction in 37 freshly frozen samples of prostate cancer tissues of a different Gleason score (GS) and at various tumor stages, compared with RE in 37 paired conventionally normal prostate tissue (CNT) samples and 20 samples of prostate adenomas. Results: Differences in RE were shown for 11 genes out of 23 studied, when tumor samples were compared with corresponding CNTs. 7 genes, namely ACTA2, CXCL14, CTGF, THY1, FAP, CD163, CCL17 were upregulated in tumors. 4 genes, namely CCR4, NOS2A, MSMB, IL1R1 were downregulated in tumors. 14 genes demonstrated different RE in TNA at different stages: CXCL12, CXCL14, CTGF, FAP, HIF1A, THY1, CCL17, CCL22, CCR4, CD68, CD163, NOS2A, CTLA4, IL1R1. RE changes of 9 genes — CXCL12, CXCL14, HIF1A, CCR4, CCL17, NOS2A, CTLA4, IL1R1, IL2RA — were found in tumors with different GS. Moreover, 9 genes showed differences in RE in TNA, dependently on the presence or absence of the TMPRSS2/ERG fusion and 7 genes showed differences in RE of groups with differential PTEN expression. Significant correlations were calculated between RE of 9 genes in adenocarcinomas and the stage, and GS; also, between RE of 2 genes and the fusion presence; and between RE of 4 genes and PTEN expression. Conclusions: Several gene expression patterns were identified that correlated with the GS, stage and molecular characteristics of tumors, i.e. presence of the TMPRSS2/ERG fusion and alterations in PTEN expression. These expression patterns can be used for molecular profiling of prostate tumors, with the aim to develop personalized medicine approaches. However, the proposed profiling requires a more detailed analysis and a larger cohort of patients with prostate tumor.

We have earlier found abnormal expression of the mitochondrial ribosomal protein S18-2 (MRPS18-2, S18-2) in endometrial cancer, compared to the expression in hyperplasia and in normal endometrium. Here we report that expression of S18-2 was increased with disease progression in clinical specimens of prostate cancer (PCa). The level of induction of epithelial to mesenchymal cell transition (EMT) correlated with the expression level of S18-2 in PCa cell lines. Moreover, cells acquired increased ability of migration upon S18-2 overexpression, as was evaluated in zebrafish embryo model and in trans-well assay. We found that this is due to increased CXCR4 cell surface expression. Neutralizing CXCR4 protein or abrogating S18-2 expression in cells significantly reduced their migratory ability directed toward CXCL12. The mRNA expression of TWIST2, encoding one of transcription factors that induce EMT upon CXCR4 increase, positively correlated with the S18-2 protein level. Together, these data suggest that the S18-2 protein induces EMT through the TWIST2/E-cadherin signalling and, consequently, CXCR4-mediated migration of PCa cells.

Aim:To analyze an expression pattern of the cancer-associated genes in prostate tumors at mRNA and protein levels and find putative association between the expression of these genes and the genes, controlling epithelial to mesenchymal cell transition (EMT), the markers of prostate cancer and stromal elements. Methods: Relative expression of genes was assessed by a quantitative PCR in 29 prostate cancer tissue samples (T) of different Gleason score (GS) and tumor stage, 29 paired conventionally normal prostate tissue (CNT) samples and in 14 samples of prostate adenomas (A). Immunohistochemistry (IHC) was used to assess protein expression. Results: We found significant differences (p < 0.05) in RE of three genes (FOS, PLAU, EPDR1) between the T, N and A groups. FOS was induced in T and CNT, compared with A whereas PLAU and EPDR1 were decreased. Noteworthy, RE of the five genes (FOS, EFNA5, TAGLN, PLAU and EPDR1) changed significantly, depending on GS (p < 0.05) in T, compared to the A and/or CNT groups. The FOS protein signal was higher in adenocarcinomas, compared to hyperplasia. The same trend was demonstrated by q-PCR. FOS expression increased upon the tumor development i.e. was higher in the tumors at stage 3-4. PLAU expression was decreasing meanwhile, as was shown by q-PCR and IHC. Conclusions: IHC data allowed us to understand the high levels of RE dispersion. Mainly, it is due to the expression in other cell types, and not in the prostate gland cells. For the meaningful clustering, prognosis and also for the creation of specific biomarker panels, these two methods should be adequately merged. 40

Aim. To determine the levels of PTEN relative expression (RE) and the possible effects of its loss on some tumor-associated genes and histological characteristics of human prostate tumors. Methods. PTEN RE and 46 genes were identified in 37 pairs of adenocarcinoma and conventionally normal tissues (CNT) and 20 adenomas by real time PCR. Results. We are shown PTEN RE decreasing in the adenocarcinoma group as well as in CNTs compared with adenomas. 54 % of adenocarcinomas, 48.6 % of CNT and 25 % of adenomas were detected with low PTEN RE. We have found 9 of 46 differentially expressed genes in groups with different levels of PTEN RE (ESR1, GCR, KRT18, MMP2, MMP9, SRD5A2, VIM, PCA3, HOTAIR). It was revealed some histological characteristics correlated with PTEN RE in prostate adenocarcinomas. Conclusions. PTEN aberrations in prostate tumors indicate that PTEN associated changes already have been occurred at the benign tumors. We have shown some tumor histological characteristics associated with PTEN expression changes.Keywords: prostate tumors, relative gene expression, PTEN, EMT, histological characteristics.