Identification of differentially expressed genes in human bladder cancer through genome-wide gene expression profiling.
Identification of differentially expressed genes in human bladder cancer through genome-wide gene expression profiling.
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DOI：
10.3892/or.16.3.521
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发表时间：
2006-09
期刊：
影响因子：
4.2
通讯作者：
Kazumori Kawakami;H. Enokida;T. Tachiwada;T. Gotanda;Kengo Tsuneyoshi;H. Kubo;K. Nishiyama;M. Takiguchi-M.
中科院分区：
文献类型：
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作者：
Kazumori Kawakami;H. Enokida;T. Tachiwada;T. Gotanda;Kengo Tsuneyoshi;H. Kubo;K. Nishiyama;M. Takiguchi-M.
大规模基因表达谱分析是了解膀胱癌 (BC) 进展的有效策略。本研究的目的是鉴定在 BC 进展过程中表达不同的基因，并建立新的 BC 生物标志物。研究人员对 21 名经病理证实的浅表性 (n = 10) 或侵袭性 (n = 11) BC 患者的标本和 4 份正常膀胱样本进行了研究；对 21 个 BC 样品中的 14 个样品进行了微阵列分析。通过实时RT-PCR验证了微阵列结果的有效性。在我们检测到的 136 个上调基因中，21 个存在于所有检查的 14 个 BC 中（100%），44 个存在于 13 个 BC 中（92.9%），其他 71 个存在于 12 个 BC 中（85.7%）。在 69 个下调基因中，在所有 14 个 BC 中发现了 25 个（100%），在 13 个 BC 中发现了 22 个（92.9%），另外 22 个在 12 个 BC 中发现（85.7%）。功能注释显示，上调基因中，36%参与代谢，14%参与转录和加工； 25% 的下调基因与细胞粘附/表面相关，21% 与细胞骨架/细胞膜相关。实时 RT-PCR 证实了 6 个最高上调基因和 2 个最高下调基因的微阵列结果。在 6 个上调最高的基因中，CKS2 是唯一一个在侵袭性 BC 中上调水平显着高于在浅表 BC 中的基因 (p = 0.04)。为了证实这一结果，我们对所有 21 个 BC 样本进行了 CKS2 实时 PCR 检测。我们发现浅表性 BC 和侵入性 BC 之间存在相当大的差异 (p = 0.001)。有趣的是，正常膀胱和侵入性 BC 之间存在相当大的差异 (p = 0.001)，而正常膀胱和浅表 BC 之间的差异较小 (p = 0.005)。我们确定了几个基因作为人类 BC 诊断生物标志物的有希望的候选者，而 CKS2 基因不仅可以作为诊断的潜在生物标志物，而且还可以作为人类 BC 分期的潜在生物标志物。这是第一份证明 CKS2 表达与人类 BC 进展密切相关的报告。
Large-scale gene expression profiling is an effective strategy for understanding the progression of bladder cancer (BC). The aim of this study was to identify genes that are expressed differently in the course of BC progression and to establish new biomarkers for BC. Specimens from 21 patients with pathologically confirmed superficial (n = 10) or invasive (n = 11) BC and 4 normal bladder samples were studied; samples from 14 of the 21 BC samples were subjected to microarray analysis. The validity of the microarray results was verified by real-time RT-PCR. Of the 136 up-regulated genes we detected, 21 were present in all 14 BCs examined (100%), 44 in 13 (92.9%), and the other 71 in 12 BCs (85.7%). Of 69 down-regulated genes, 25 were found in all 14 BCs (100%), 22 in 13 (92.9%), and the other 22 in 12 BCs (85.7%). Functional annotation revealed that of the up-regulated genes, 36% were involved in metabolism and 14% in transcription and processing; 25% of the down-regulated genes were linked to cell adhesion/surface and 21% to cytoskeleton/cell membrane. Real-time RT-PCR confirmed the microarray results obtained for the 6 most highly up- and the 2 most highly down-regulated genes. Among the 6 most highly up-regulated genes, CKS2 was the only gene with a significantly greater level of up-regulation in invasive than in superficial BC (p = 0.04). To confirm this result, we subjected all 21 BC samples to real-time PCR assay for CKS2. We found a considerable difference between superficial and invasive BC (p = 0.001). Interestingly, there was a considerable difference between the normal bladder and invasive BC (p = 0.001) and less difference between the normal bladder and superficial BC (p = 0.005). We identified several genes as promising candidates for diagnostic biomarkers of human BC and the CKS2 gene not only as a potential biomarker for diagnosing, but also for staging human BC. This is the first report demonstrating that CKS2 expression is strongly correlated with the progression of human BC.