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首页> 外文期刊>British Journal of Cancer >Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM
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Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM

机译：尿路上皮癌中的蛋白质脱落：可溶性尿EGFR和EpCAM对预后的影响

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Background: Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests. Methods: We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up. Results: Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81–4.62, P <0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations. Conclusions: Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.
机译：背景：必须发现更好的生物标记物才能开发出对膀胱癌具有临床意义的尿液检测方法。蛋白质组学可用于鉴定癌细胞系释放的蛋白质，并生成用于进行此类检测的候选标记。方法：我们使用shot弹枪蛋白质组学来鉴定八种膀胱癌细胞系释放到培养基中的蛋白质。将这些数据与人类蛋白质图谱的蛋白质表达数据进行了比较。表皮生长因子受体（EGFR）被鉴定为候选生物标志物，并通过ELISA在来自60位非癌对照受试者以及436名患有膀胱癌和长期临床随访的患者的尿液中进行了测量。结果：膀胱癌细胞系脱落了可溶性EGFR胞外域。在尿液中也可检测到可溶性EGFR，在某些患有高度膀胱癌的患者中，EGFR高度升高。尿EGFR是膀胱癌特异性生存不良的独立指标，危险比为2.89（95％CI 1.81–4.62，P <0.001）。在包括尿EGFR和EpCAM在内的多变量模型中，这两种生物标志物都可以预测膀胱癌的特异性生存，并且具有比标准临床观察结果更高的预后价值。结论：测量尿EGFR和EpCAM可能代表一种简单而有用的方法，用于快速追踪最具侵略性膀胱癌的患者的调查和治疗。

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