Laboratory of Medical Investigation, LIM 55, Division of Urology, University of Sao Paulo Medical School, São Paulo, Brazil.
Urol Oncol. 2012 Jan-Feb;30(1):16-20. doi: 10.1016/j.urolonc.2009.09.014. Epub 2009 Nov 27.
By reason of its heterogeneous behavior, it is difficult to determine the prognosis of many prostate cancer cases. Patients with the same clinicopathologic conditions may present varying clinical findings and rates of progression. We determined the role of new genes as potential molecular markers for prostate cancer prognosis.
We performed a microarray analysis of two pools of patients with prostate cancer divided according to their clinicopathologic characteristics. After that, we validated these results by testing the genes with most different expressions between the two pools using the quantitative real time polymerase chain reaction method. We analyzed gene expression in 33 patients with localized prostate cancer according to prostate specific antigen (PSA), pathologic stage, Gleason score, and biochemical recurrence. For statistical analysis we used the Mann-Whitney Test.
The microarray analysis revealed that 4,147 genes presented a different expression between the two pools. Among them, 3 genes, TMEFF2, GREB1, and TH1L, were at least 13-times overexpressed, and 1 gene, IGH3, which was at least 5 times under-expressed in pool 1 (good prognosis) compared with pool 2 (bad prognosis), were selected for analysis. After the validation tests, GREB1 was significantly more overexpressed among patients with stage T2 compared with T3 (P = 0.020). The expressions of other 3 genes did not present significant differences according to the clinicopathological variables.
Tissue expression of GREB1 is associated with organ-confined prostate cancer and may constitute a gene associated with a favorable prognosis.
由于其异质性的行为，许多前列腺癌病例的预后难以确定。具有相同临床病理条件的患者可能表现出不同的临床发现和进展率。我们确定了新基因作为前列腺癌预后潜在分子标志物的作用。
我们对根据临床病理特征分为两组的前列腺癌患者进行了微阵列分析。之后，我们使用定量实时聚合酶链反应方法测试了两个池之间表达差异最大的基因，验证了这些结果。我们根据前列腺特异性抗原（PSA）、病理分期、Gleason 评分和生化复发情况，分析了 33 例局限性前列腺癌患者的基因表达。统计分析采用 Mann-Whitney 检验。
微阵列分析显示，两组之间有 4147 个基因表达不同。其中，TMEFF2、GREB1 和 TH1L 这 3 个基因在池 1（预后良好）中的表达至少是池 2（预后不良）的 13 倍，IGH3 基因在池 1 中的表达至少是池 2 的 5 倍，选择用于分析。经过验证试验，GREB1 在 T2 期患者中的表达明显高于 T3 期（P = 0.020）。其他 3 个基因的表达与临床病理变量无显著差异。
GREB1 的组织表达与器官局限性前列腺癌相关，可能构成与预后良好相关的基因。
