Expression of epithelial-mesenchymal transition-related genes in prostate tumours

Abstract

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.

Expression of cancer-associated genes in prostate tumors at mRNA and protein levels

“…[The] Clinicopathological characteristics (CPC) of adenocarcinomas and the presence and/or absence of the TMPRSS2/ERG fusion that was reported by us earlier [1,21] are presented in Table 1.…”

“…Besides alteration of the expression pattern of the described seven genes, we found that the prostate-specific genes [19] and the tumor stromal elements [20] show differential expression in the tissues samples of prostate cancer, compared with the benign tumors. Also, the expression of genes, involved in EMT was altered [21], and in a proportion of prostate tumors the presence of the TMPRSS2:ERG fusion was detected [22].…”

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“…All samples were collected in accordance with the Declaration of Helsinki and the guidelines, issued by an Ethic Committee of the Institute of Urology of National Academy of Medical Sciences of Ukraine and of the National Cancer Institute of National Academy of Sciences of Ukraine (NASU), and the Ethic Committee of the Institute of Molecular biology and genetics of NASU. Experimental studies were conducted, using 37 prostate adenocarcinoma samples of different Gleason scores and at various stages; 37 corresponding conventional normal tissue (CNT) samples; and 20 samples of adenomas [10,11]. The tumor samples were characterized, according to the International System of Classification of Tumors, based on the tumor-node-metastasis (TNM) and the World Health Organization (WHO) criteria.…”

“…The tumor samples were characterized, according to the International System of Classification of Tumors, based on the tumor-node-metastasis (TNM) and the World Health Organization (WHO) criteria. The clinical characteristics of the tumors were described earlier [10,11].…”

“…RE levels were calculated, using two common methods (2 -ΔCt and 2 -ΔΔCt ) described earlier [10][11][12].…”