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[PCA3和TMPRSS2:ERG基因在良性前列腺增生、上皮内瘤变和前列腺癌活检组织中的表达]

[PCA3 AND TMPRSS2:ERG GENES EXPRESSION IN BIOPSIES OF BENIGN PROSTATE HYPERPLASIA, INTRAEPITHELIAL NEOPLASIA, AND PROSTATE CANCER].

作者信息

Mikhaylenko D S, Perepechin D V, Grigoryeva M V, Zhinzhilo T A, Safronova N Yu, Efremov G D, Sivkov A V

出版信息

Urologiia. 2015 Sep-Oct(5):46-50.

Abstract

Morphological analysis of the biopsies for prostate cancer (PCa) often is a difficult task due to heterogeneity and multifocality of tumors. At the same time, a lot of data exist about the potential molecular genetic markers of PCa. The aim of our study is to determine of PCA3 and TMPRSS2:ERG genes expression in benign hyperplasia (BPH), low and high grade intraepithelial neoplasia (PIN), PCa for revealing of diagnostic value of those genes expression in benign and precancerous changes in prostate. Total RNA was isolated from 53 biopsies, reverse transcription was performed, gene expression was determined by real time PCR (RT-PCR) then deltaCt index was determined as Ct(PCA3)--Ct(KLK3). Average deltaCt and its SD in BPH were 8.28 ± 3.13, low PIN--8.56 ± 2.64, high PIN--8.98 ±1.69, PCa--1.08 ± 2.36. We have demonstarted that deltaCt did not differ in patients with BPH, low and high grade PIN, whereas significantly increased in PCa relative to any of the three groups listed above (p < 0.0001). Expression of TMPRSS2:ERG was absent in BPH, PIN, but it was detected in 40% (4/10) of PCa cases. ROC-analysis showed that the AUC (area under ROC-curve with 95% CI, p < 0.0001) was 0.98 ± 0.02 in the analysis of a combination of overexpression of PCA3 and TMPRSS2:ERG. Thus, the expression analysis of the PCA3 and chimeric oncogene TMPRSS2:ERG in biopsy cannot be used for differential diagnosis of BPH, low and high grade PIN. However, overexpression of PCA3 and expression of TMPRSS2:ERG are characteristic in PCa. Expression analysis of these genes by the proposed RT-PCR modification at the threshold level deltaCt 3,22 has diagnostic accuracy 90% to detect PCa in biopsy specimens.

摘要

由于前列腺癌(PCa)肿瘤的异质性和多灶性,对其活检进行形态学分析往往是一项艰巨的任务。与此同时,关于PCa潜在分子遗传标志物的资料很多。我们研究的目的是确定PCA3和TMPRSS2:ERG基因在良性前列腺增生(BPH)、低级别和高级别上皮内瘤变(PIN)、PCa中的表达情况,以揭示这些基因表达在前列腺良性和癌前病变中的诊断价值。从53份活检样本中提取总RNA,进行逆转录,通过实时PCR(RT-PCR)测定基因表达,然后将deltaCt指数确定为Ct(PCA3)-Ct(KLK3)。BPH组的平均deltaCt及其标准差为8.28±3.13,低级别PIN组为8.56±2.64,高级别PIN组为8.98±1.69,PCa组为1.08±2.36。我们已经证明,BPH、低级别和高级别PIN患者的deltaCt没有差异,而相对于上述三组中的任何一组,PCa患者的deltaCt显著增加(p<0.0001)。BPH、PIN中未检测到TMPRSS2:ERG的表达,但在40%(4/10)的PCa病例中检测到。ROC分析表明,在分析PCA3过表达和TMPRSS2:ERG组合时,AUC(95%CI的ROC曲线下面积,p<0.0001)为0.98±0.02。因此,活检中PCA3和嵌合癌基因TMPRSS2:ERG的表达分析不能用于BPH、低级别和高级别PIN的鉴别诊断。然而,PCA3过表达和TMPRSS2:ERG表达是PCa的特征。通过所提出的RT-PCR修饰在deltaCt阈值水平为3.22时对这些基因进行表达分析,在活检标本中检测PCa的诊断准确率为90%。

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