Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma.
Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma.
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DOI：
10.1038/bjc.2013.157
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发表时间：
2013-05-14
影响因子：
8.8
通讯作者：
Ward DG
中科院分区：
文献类型：
--
作者：
Shimwell NJ;Bryan RT;Wei W;James ND;Cheng KK;Zeegers MP;Johnson PJ;Martin A;Ward DG
蛋白质组学发现体液中的癌症生物标记物具有挑战性，因为它们在复杂的背景下丰度很低。肿瘤中基因表达的改变可能不会反映体液中的蛋白质水平。我们已经测试了结合肿瘤的基因表达谱和癌细胞系分泌体的蛋白质组学分析作为发现膀胱癌的尿液生物标记物的策略。我们用鸟枪式蛋白质组学方法鉴定了三种膀胱癌细胞株分泌的蛋白质。用双抗体夹心法检测了642例膀胱肿瘤患者尿液标本中相对正常尿路上皮高水平的分泌蛋白。中期因子和HAI-1在膀胱癌患者中显著升高，在浸润性疾病中水平最高(受试者工作特征曲线下面积与非癌症患者相比为0.89)。这两种蛋白的尿液浓度太高，不能用膀胱癌相关性血尿来解释，很可能是由肿瘤直接分泌引起的。这种“双组体”策略确定了肿瘤分泌蛋白，其尿液浓度因膀胱癌而显著增加。对于膀胱癌和其他肿瘤类型的生物标记物的发现，联合分泌组-转录组分析可能比直接的体液蛋白质组学分析更有用。
Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer. We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients. Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89 vs non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion. This ‘dual-omic' strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour types.
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