前列腺肿瘤上皮-间质转化相关基因的表达

G. Gerashchenko, O. Mankovska, A. Dmitriev, L. Mevs, E. E. Rosenberg, M. Pikul, M. V. Marynychenko, O. Gryzodub, E. Stakhovsky, V. Kashuba
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引用次数: 13

摘要

的目标。检测前列腺肿瘤样本中emt相关基因的表达,分析不同组前列腺癌临床特征与基因表达水平的可能相关性。方法。采用定量PCR方法,对37例不同肿瘤分期及Gleason评分的前列腺癌组织冷冻标本、37对常规正常前列腺组织和20例前列腺腺瘤标本中19个基因的表达进行分析。结果。我们发现在前列腺良恶性肿瘤中有9个基因表达不同,分别是AR(亚型1)、AR(亚型2)、PTEN、VIM、MMP9、KRT18、PCA3、HOTAIR和SCHLAP1。通过对不同肿瘤分期的比较,我们鉴定出6个差异表达基因:KRT18、MMP9、VIM、PCA3、HOTAIR和SCHLAP1;对比不同Gleason评分的肿瘤样本,我们发现AR (isoform 1)、CDH1、KRT18、MMP9、OCLN、PCA3、HOTAIR和SCHLAP1这8个基因的表达存在差异。数据具有高度的异质性,可能是由于前列腺癌的不同分子亚型,即CDH1、OCLN、AR(1 isof)、KRT18、NKX3-1和PSA高表达的管腔亚型;茎样亚型,间充质标志物CDH2、FN1和VIM高表达,上皮标志物低表达。值得注意的是,lncrna在这两种分子亚型中均有特异性表达。结论。emt相关基因在前列腺良恶性肿瘤中的表达存在差异。表达水平的高度异质性,特别是在腺癌组中,可能表明存在至少两种不同的分子亚型,管腔型和茎样型。需要进一步的实验来明确前列腺腺癌的分子亚型。
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Expression of epithelial-mesenchymal transition-related genes in prostate tumours
Aim. 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.
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