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用于早期诊断肾癌的尿液生物标志物。

Urinary biomarkers for the early diagnosis of kidney cancer.

机构信息

Department of Anesthesiology, Division of Clinical and Translational Research, Campus Box 8054, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110-1093, USA.

出版信息

Mayo Clin Proc. 2010 May;85(5):413-21. doi: 10.4065/mcp.2009.0709. Epub 2010 Apr 7.

Abstract

OBJECTIVE

To test the hypothesis that increased tumor expression of proteins such as aquaporin-1 (AQP1) and adipophilin (ADFP) in patients with renal cancer would result in increased urine AQP1 and ADFP excretion.

PATIENTS AND METHODS

Prenephrectomy and postnephrectomy (pseudocontrol) urine samples were collected from 42 patients with an incidental radiographically discovered renal mass and presurgical presumptive diagnosis of kidney cancer from July 8, 2008, through March 10, 2009. Also enrolled were 15 control patients who underwent nonrenal surgery and 19 healthy volunteers. Urine AQP1 and ADFP concentrations normalized to urine creatinine were determined by sensitive and specific Western blot assays.

RESULTS

Mean +/- SD preexcision urine AQP1 and ADFP concentrations (76+/-29 and 117+/-74 arbitrary units, respectively) in patients with a pathologic diagnosis of clear cell (n=22) or papillary (n=10) cancer were significantly greater than in patients with renal cancer of nonproximal tubule origin, control surgical patients, and healthy volunteers (combined values of 0.1+/-0.1 and 1.0+/-1.6 arbitrary units, respectively; n=44; P<.001). The AQP1 and ADFP concentrations decreased 88% to 97% in the 25 patients with clear cell or papillary cancer who provided postnephrectomy follow-up urine samples. In patients with clear cell and papillary carcinoma, a linear correlation (Spearman) was found between tumor size and preexcision urine AQP1 or ADFP concentration (r=0.82 and 0.76, respectively; P<.001 for each).

CONCLUSION

Urine AQP1 and ADFP concentrations appear to be sensitive and specific biomarkers of kidney cancers of proximal tubule origin. These biomarkers may be useful to diagnose an imaged renal mass and screen for kidney cancer at an early stage.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00851994.

摘要

目的

验证假设,即肾癌细胞中水通道蛋白-1(AQP1)和脂滴包被蛋白(ADFP)等蛋白的肿瘤表达增加,将导致尿液 AQP1 和 ADFP 排泄增加。

患者和方法

2008 年 7 月 8 日至 2009 年 3 月 10 日,共纳入 42 例偶然发现的有影像学表现的肾占位患者和术前假定为肾癌的患者的术前和术后(假性对照)尿样。还纳入了 15 例接受非肾脏手术的对照患者和 19 例健康志愿者。采用敏感和特异的 Western blot 法测定尿 AQP1 和 ADFP 浓度,并用尿肌酐进行标准化。

结果

病理诊断为透明细胞癌(n=22)或乳头状癌(n=10)的患者术前尿 AQP1 和 ADFP 浓度(分别为 76+/-29 和 117+/-74 个任意单位)显著高于肾非近端小管来源癌患者、对照手术患者和健康志愿者(分别为 0.1+/-0.1 和 1.0+/-1.6 个任意单位;n=44;P<.001)。25 例提供术后随访尿样的透明细胞癌或乳头状癌患者,尿 AQP1 和 ADFP 浓度分别下降 88%至 97%。在透明细胞癌和乳头状癌患者中,肿瘤大小与术前尿 AQP1 或 ADFP 浓度呈线性相关(Spearman 相关系数分别为 0.82 和 0.76;P<.001)。

结论

尿 AQP1 和 ADFP 浓度似乎是近端肾小管来源肾癌的敏感和特异的生物标志物。这些生物标志物可能有助于诊断影像学检查的肾占位并在早期筛查肾癌。

试验注册

clinicaltrials.gov 标识符:NCT00851994。

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