Novel blood biomarkers of human urinary bladder cancer
Novel blood biomarkers of human urinary bladder cancer
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DOI：
10.1158/1078-0432.ccr-05-2081
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发表时间：
2006-06-01
影响因子：
11.5
通讯作者：
Liew, CC
中科院分区：
文献类型：
--
作者：
Osman, I;Bajorin, DF;Liew, CC
目的：最新数据表明，血细胞cDNA微阵列基因表达谱可以反映疾病状态，因而具有诊断价值。我们测试了血细胞基因表达可以区分膀胱癌和其他泌尿生殖系统癌症以及膀胱癌和健康对照的假设。实验设计：我们使用 Affymetrix U133 Plus 2.0 GeneChip (Affymetrix, Santa Clara, CA) 分析 35 名被诊断患有三种类型泌尿生殖系统癌症之一的患者的循环血液总 RNA [膀胱癌 (n = 16)、睾丸癌] (n = 10) 和肾细胞癌 (n = 9)] 并将其 cDNA 谱与 10 名健康受试者的 cDNA 谱进行比较。然后，我们验证了 Affymetrix 结果中选定基因在大量膀胱癌患者 (n = 40) 和健康对照 (n = 27) 中的表达水平。结果：血液基因表达谱将膀胱癌患者与健康对照以及睾丸癌和肾癌患者区分开来。七个基因转录本（胰岛素样生长因子 - 结合蛋白 7、分选连接蛋白 16、硫酸软骨素蛋白聚糖 6 和组织蛋白酶 D、色域解旋酶 DNA 结合蛋白 2、nell 样 2 和肿瘤坏死因子受体超家族成员 7）组合的差异表达能够灵敏地将膀胱癌与对照样本区分开来 83%（95% 置信区间，67-93%）和 93%（95% 置信区间，76-99%）的特异性。结论：我们已经证明，循环血细胞的基因表达谱可以区分膀胱癌与其他类型的泌尿生殖系统癌症和健康对照，并可用于识别膀胱癌的新型血液标志物。
Purpose: Recent data indicate that cDNA microarray gene expression profile of blood cells can reflect disease states and thus have diagnostic value. We tested the hypothesis that blood cell gene expression can differentiate between bladder cancer and other genitourinary cancers as well as between bladder cancer and healthy controls.Experimental Design: We used Affymetrix U133 Plus 2.0 GeneChip (Affymetrix, Santa Clara, CA) to profile circulating blood total RNA from 35 patients diagnosed with one of three types of genitourinary cancer [bladder cancer (n = 16), testicular cancer (n = 10), and renal cell carcinoma (n = 9)] and compared their cDNA profiles with those of 10 healthy subjects. We then verified the expression levels of selected genes from the Affymetrix results in a larger number of bladder cancer patients (n = 40) and healthy controls (n = 27).Results: Blood gene expression profiles distinguished bladder cancer patients from healthy controls and from testicular and renal cancer patients. Differential expression of a combined set of seven gene transcripts (insulin-like growth factor - binding protein 7, sorting nexin 16, chondroitin sulfate proteoglycan 6, and cathepsin D, chromodomain helicase DNA-binding protein 2, nell-like 2, and tumor necrosis factor receptor superfamily member 7) was able to discriminate bladder cancer from control samples with a sensitivity of 83% (95% confidence interval, 67-93%) and a specificity of 93% (95% confidence interval, 76-99%).Conclusion: We have shown that the gene expression profile of circulating blood cells can distinguish bladder cancer from other types of genitourinary cancer and healthy controls and can be used to identify novel blood markers for bladder cancer.