DNA Microarray Expression Profiling of Bladder Cancer Allows Identification of Noninvasive Diagnostic Markers
DNA Microarray Expression Profiling of Bladder Cancer Allows Identification of Noninvasive Diagnostic Markers
复制标题
DOI：
10.1016/j.juro.2009.03.084
复制
发表时间：
2009-08-01
影响因子：
6.6
通讯作者：
Alcaraz, Antonio
中科院分区：
文献类型：
--
作者：
Mengual, Lourdes;Burset, Moises;Alcaraz, Antonio
目的：泌尿外科实践需要鉴定新的膀胱癌分子标志物，以进一步开发无创诊断测试。我们分析了膀胱癌基因表达谱，以确定相关的差异表达基因以及这种差异表达是否在尿液样本中维持。材料和方法：我们收集了 2003 年 9 月至 2004 年 12 月期间总共 43 名膀胱癌患者和 12 名对照者的 55 份组织标本，以及来自总共 36 名膀胱癌患者和 13 名对照者的膀胱冲洗液的 49 份尿液样本。DNA 微阵列（GeneChip (R) Human Genome U133） Plus 2.0 Array）用于鉴定膀胱癌3个阶段的差异表达基因。通过定量逆转录酶-聚合酶链式反应在一组独立的膀胱冲洗液中验证选定的差异表达基因。结果：DNA 微阵列数据的无监督聚类分析显示对照与肿瘤样本以及低级别肿瘤与高级别肿瘤之间存在明显区别。对照与肿瘤（2,937 个探针组或 2,295 个基因）以及低级别肿瘤与高级别肿瘤（674 个探针组或 530 个基因）中至少有 2 倍差异表达的基因被鉴定和排序。通过定量逆转录酶-聚合酶链反应测试的 2 个过表达基因，证实了对照与肿瘤中 6 个差异最大的基因在膀胱冲洗液中的基因表达测量。所有 8 个选定的低级别肿瘤与高级别肿瘤中的差异表达基因均在膀胱冲洗样本中得到证实。结论：通过 DNA 微阵列进行的膀胱癌分析为膀胱癌诊断和/或预后提供了新的推定 mRNA 标记，这些标记可以外推至膀胱液。
Purpose: There is a need in urological practice to identify new bladder cancer molecular markers to further develop noninvasive diagnostic tests. We analyzed bladder cancer gene expression profiles to determine the relevant differentially expressed genes and whether this differential expression is maintained in urine samples.Materials and Methods: We collected 55 tissue specimens from a total of 43 patients with bladder cancer and 12 controls, and 49 urine samples from bladder washings from a total of 36 patients with bladder cancer and 13 controls between September 2003 and December 2004. DNA microarrays (GeneChip (R) Human Genome U133 Plus 2.0 Array) were used to identify differentially expressed genes at 3 bladder cancer stages. Selected differentially expressed genes were validated in an independent set of bladder washings by quantitative reverse transcriptase-polymerase chain reaction.Results: Unsupervised cluster analysis of DNA microarray data showed a clear distinction in control vs tumor samples and low vs high grade tumors. Genes with at least 2-fold differential expression in controls vs tumors (2,937 probe sets or 2,295 genes) and in low vs high grade tumors (674 probe sets or 530 genes) were identified and ranked. Gene expression measurements in bladder washings of the 6 most differentially expressed genes in controls vs tumors were confirmed for the 2 over expressed genes tested by quantitative reverse transcriptase-polymerase chain reaction. All 8 selected differentially expressed genes in low vs high grade tumors were confirmed in bladder washing samples.Conclusions: Bladder cancer analysis by DNA microarrays provides new putative mRNA markers for bladder cancer diagnosis and/or prognosis that can be extrapolated to bladder fluids.