Varambally Sooryanarayana, Laxman Bharathi, Mehra Rohit, Cao Qi, Dhanasekaran Saravana M, Tomlins Scott A, Granger Jill, Vellaichamy Adaikkalam, Sreekumar Arun, Yu Jianjun, Gu Wenjuan, Shen Ronglai, Ghosh Debashis, Wright Lorinda M, Kladney Raleigh D, Kuefer Rainer, Rubin Mark A, Fimmel Claus J, Chinnaiyan Arul M
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Neoplasia. 2008 Nov;10(11):1285-94. doi: 10.1593/neo.08922.
Prostate cancer is the most common type of tumor found in American men and is the second leading cause of cancer death in males. To identify biomarkers that distinguish prostate cancer from normal, we compared multiple gene expression profiling studies. Through meta-analysis of expression array data from multiple prostate cancer studies, we identified GOLM1 (Golgi membrane protein 1, Golm 1) as consistently up-regulated in clinically localized prostate cancer. This observation was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and validated at the protein level by immunoblot assay and immunohistochemistry. Prostate epithelial cells were identified as the cellular source of GOLM1 expression using laser capture microdissection. Immunohistochemical staining localized the GOLM1 signal to the subapical cytoplasmic region, typical of a Golgi distribution. Surprisingly, GOLM1 immunoreactivity was detected in the supernatants of prostate cell lines and in the urine of patients with prostate cancer. The mechanism by which intact GOLM1 might be released from cells has not yet been elucidated. GOLM1 transcript levels were measured in urine sediments using quantitative PCR on a cohort of patients presenting for biopsy or radical prostatectomy. We found that urinary GOLM1 mRNA levels were a significant predictor of prostate cancer. Further, GOLM1 outperformed serum prostate-specific antigen (PSA) in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.622 for GOLM1 (P = .0009) versus 0.495 for serum PSA (P = .902). Our data indicating the up-regulation of GOLM1 expression and its appearance in patients' urine suggest GOLM1 as a potential novel biomarker for clinically localized prostate cancer.
前列腺癌是美国男性中最常见的肿瘤类型,也是男性癌症死亡的第二大主要原因。为了识别区分前列腺癌与正常组织的生物标志物,我们比较了多项基因表达谱研究。通过对多项前列腺癌研究的表达阵列数据进行荟萃分析,我们发现高尔基体膜蛋白1(GOLM1)在临床局限性前列腺癌中持续上调。这一观察结果通过逆转录-聚合酶链反应(RT-PCR)得到证实,并在蛋白质水平通过免疫印迹分析和免疫组织化学进行了验证。使用激光捕获显微切割技术确定前列腺上皮细胞是GOLM1表达的细胞来源。免疫组织化学染色将GOLM1信号定位到顶端下细胞质区域,这是典型的高尔基体分布。令人惊讶的是,在前列腺癌细胞系的上清液和前列腺癌患者的尿液中检测到了GOLM1免疫反应性。完整的GOLM1从细胞中释放的机制尚未阐明。使用定量PCR对一组进行活检或根治性前列腺切除术的患者的尿沉渣中GOLM1转录水平进行了测量。我们发现尿中GOLM1 mRNA水平是前列腺癌的一个重要预测指标。此外,在检测前列腺癌方面,GOLM1优于血清前列腺特异性抗原(PSA)。GOLM1的受试者操作特征曲线下面积为0.622(P = .0009),而血清PSA为0.495(P = .902)。我们的数据表明GOLM1表达上调及其在患者尿液中的出现提示GOLM1可能是临床局限性前列腺癌的一种潜在新型生物标志物。