Department of Clinical and Molecular Pathology, Laboratory of Molecular Pathology, Institute of Molecular and Translational Medicine, Palacky University and University Hospital, Olomouc, Czech Republic.
Prostate Cancer Prostatic Dis. 2011 Dec;14(4):354-60. doi: 10.1038/pcan.2011.32. Epub 2011 Jul 26.
The major advantages of urine-based assays are their non-invasive character and ability to monitor prostate cancer (CaP) with heterogeneous foci. While the test for the prostate cancer antigen 3 (PCA3) is commercially available, the aim of our research was to test other putative urine markers in multiplex settings (AMACR (α-methylacyl-CoA racemase), EZH2 (enhancer of zeste homolog 2), GOLM1 (golgi membrane protein 1), MSMB (microseminoprotein, β), SPINK1 (serine peptidase inhibitor) and TRPM8 (transient receptor potential cation channel, subfamily M, member 8)).
Expression of the candidate biomarkers was studied in sedimented urine using quantitative reverse transcriptase polymerase chain reaction in two sets of patients with and without restriction on serum PSA levels.
We confirmed that PCA3 is an independent predictor of cancer in the patients without restriction of serum PSA values (set 1, n=176, PSA=0.1-587 ng ml(-1)). However, AMACR was the only parameter that differentiated CaP from non-CaP patients with serum PSA between 3 and 15 ng ml(-1) (set 2, n=104). The area under curve (AUC) for this gene was 0.645 with both sensitivity and specificity at 65%. Further improvement was achieved by multivariate logistic regression analysis, which identified novel duplex (TRPM8 and MSMB), triplex (plus AMACR) and quadriplex (plus PCA3) models for the detection of early CaPs (AUC=0.665, 0.726 and 0.741, respectively).
Novel quadriplex test could be implemented as an adjunct to serum PSA or urine PCA3 and this could improve decision making for diagnostics in the case of 'PSA dilemma' patients.
尿液检测的主要优势在于其非侵入性，以及能够监测具有异质性病灶的前列腺癌（CaP）。虽然前列腺癌抗原 3（PCA3）检测已经商业化，但我们的研究目的是在多重检测环境中测试其他潜在的尿液标志物（α-甲基酰基辅酶 A racemase（AMACR）、增强子结合抑制因子 2（EZH2）、高尔基膜蛋白 1（GOLM1）、β-微精囊蛋白（MSMB）、丝氨酸蛋白酶抑制剂（SPINK1）和瞬时受体电位阳离子通道亚家族 M 成员 8（TRPM8））。
使用定量逆转录聚合酶链反应（qRT-PCR）在两组患者（一组有血清 PSA 水平限制，一组无血清 PSA 水平限制）的沉淀尿液中研究候选生物标志物的表达情况。
我们证实 PCA3 是无血清 PSA 限制患者癌症的独立预测因子（组 1，n=176，PSA=0.1-587ng/ml）。然而，只有 AMACR 能够区分血清 PSA 为 3-15ng/ml 的 CaP 与非 CaP 患者（组 2，n=104）。该基因的曲线下面积（AUC）为 0.645，灵敏度和特异性均为 65%。通过多元逻辑回归分析进一步改善，该分析确定了用于检测早期 CaP 的新的二联（TRPM8 和 MSMB）、三联（加 AMACR）和四联（加 PCA3）模型（AUC 分别为 0.665、0.726 和 0.741）。
新的四联检测可作为血清 PSA 或尿液 PCA3 的辅助手段，这可能会改善“PSA 困境”患者的诊断决策。
