Fuessel Susanne, Sickert Denise, Meye Axel, Klenk Ulrich, Schmidt Uta, Schmitz Marc, Rost Anne-Katrin, Weigle Bernd, Kiessling Andrea, Wirth Manfred P
Department of Urology, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany.
Int J Oncol. 2003 Jul;23(1):221-8.
The identification of new diagnostic markers and potential treatment targets for prostate carcinoma (PCa) necessitates the evaluation of expression patterns in both malignant and non-malignant tissue specimens. In this study, we compared the mRNA expression of recently identified prostate-associated genes, prostate stem cell antigen (PSCA) and transient receptor potential p8 (trp-p8), to the mRNA expression of the most commonly used markers for PCa, prostate-specific antigen (PSA) and human kallikrein 2 (hK2). For these four candidates we performed highly specific quantitative real-time LightCycler RT-PCR assays with cDNA originating from matched tissue specimens of 40 patients with primary PCa. The highest transcript amounts were found for PSA in malignant as well as in non-malignant tissue specimens followed by hK2, trp-p8 and PSCA with an mRNA expression remarkably lower. The relative transcript levels of PSA, hK2 and trp-p8 were elevated in malignant in comparison to non-malignant tissues, but only for trp-p8 this increased expression was statistically significant. Focussing on organ confined tumors, we found a significant difference of the mRNA expression of PSA and trp-p8 between malignant and non-malignant tissue specimens. The marker trp-p8 is also suited to differentiate between the tumor stages when quantifying its transcript levels within tumor tissue specimens. The evaluation of the mRNA expression patterns of these markers by quantitative real-time RT-PCR could provide new tools for differential diagnosis and molecular staging. According to our data, the novel marker trp-p8 seems to represent a highly prostate-specific and PCa-associated gene qualifying it as a potential target for specific therapies.
鉴定前列腺癌(PCa)的新诊断标志物和潜在治疗靶点需要评估恶性和非恶性组织标本中的表达模式。在本研究中,我们将最近鉴定出的前列腺相关基因前列腺干细胞抗原(PSCA)和瞬时受体电位p8(trp-p8)的mRNA表达与PCa最常用标志物前列腺特异性抗原(PSA)和人激肽释放酶2(hK2)的mRNA表达进行了比较。对于这四个候选物,我们使用来自40例原发性PCa患者匹配组织标本的cDNA进行了高度特异性的定量实时LightCycler RT-PCR分析。在恶性和非恶性组织标本中,PSA的转录本含量最高,其次是hK2、trp-p8和PSCA,其mRNA表达明显较低。与非恶性组织相比,PSA、hK2和trp-p8的相对转录水平在恶性组织中升高,但只有trp-p8的这种表达增加具有统计学意义。聚焦于器官局限性肿瘤,我们发现恶性和非恶性组织标本中PSA和trp-p8的mRNA表达存在显著差异。当在肿瘤组织标本中定量trp-p8的转录水平时,该标志物也适用于区分肿瘤分期。通过定量实时RT-PCR评估这些标志物的mRNA表达模式可为鉴别诊断和分子分期提供新工具。根据我们的数据,新型标志物trp-p8似乎是一个高度前列腺特异性且与PCa相关的基因,使其有资格成为特异性治疗的潜在靶点。