Evaluation of Urine Aquaporin-1 and Perilipin-2 Concentrations as Biomarkers to Screen for Renal Cell Carcinoma: A Prospective Cohort Study.
Evaluation of Urine Aquaporin-1 and Perilipin-2 Concentrations as Biomarkers to Screen for Renal Cell Carcinoma: A Prospective Cohort Study.
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DOI：
10.1001/jamaoncol.2015.0213
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发表时间：
2015-05
期刊：
影响因子：
28.4
通讯作者：
Kharasch ED
中科院分区：
文献类型：
--
作者：
Morrissey JJ;Mellnick VM;Luo J;Siegel MJ;Figenshau RS;Bhayani S;Kharasch ED
早期发现小的无症状肾肿瘤预示着更好的患者预后。通过腹部成像偶然发现无症状肾肿瘤的费用昂贵，并且不能可靠地区分良性肿瘤和恶性肿瘤。这项研究评估了尿液水通道蛋白-1 (AQP1) 和 perilipin-2 (PLIN2) 浓度作为独特的非侵入性生物标志物在筛查范式中诊断恶性透明细胞癌或乳头状肾细胞癌 (RCC) 的临床实用性、敏感性和特异性。尿液样本取自 720 名接受常规腹部 CT 的患者（筛查人群）、80 名健康对照者和 19 名经病理证实的肾细胞癌患者。尿液 AQP1 和 PLIN2 浓度分别通过敏感和特异性 ELISA 和蛋白质印迹程序测量。在无症状人群的筛查范式中前瞻性测量 AQP1 和 PLIN2。分别通过腹部计算机断层扫描（CT）和肾切除术后病理诊断来验证是否存在肾脏肿块和肾细胞癌。已知 RCC 患者的中位尿液 AQP1 和 PLIN2 浓度比对照和筛查人群高 12 倍以上（均 P<0.0001）。尿液 AQP1 和 PLIN2 浓度单独或组合的受试者工作特征曲线下面积≥0.92，与对照或筛查患者相比，敏感性≥85%，特异性≥87%。 720 名筛查患者中，有 3 名的生物标志物浓度提示肾细胞癌，并通过 CT 成像发现肾脏肿块。经进一步评估，两名患者患有肾细胞癌。这些结果证明了尿液 AQP1 和 PLIN2 诊断 RCC 的临床实用性、特异性和敏感性。这些新型肿瘤特异性蛋白具有很高的临床有效性和巨大潜力，可作为透明细胞和乳头状肾细胞癌的特异性诊断和筛查生物标志物，以及影像学肾肿块的鉴别诊断。
Early detection of small asymptomatic kidney tumors presages better patient outcome. Incidental discovery of asymptomatic renal tumors by abdominal imaging is expensive and cannot reliably distinguish benign from malignant tumors. This investigation evaluated the clinical utility, sensitivity and specificity of urine aquaporin-1 (AQP1) and perilipin-2 (PLIN2) concentrations as unique noninvasive biomarkers to diagnose malignant clear cell or papillary renal cell carcinoma (RCC) in a screening paradigm. Urine samples were obtained from 720 patients undergoing routine abdominal CT (screening population), 80 healthy controls and 19 patients with pathologically confirmed RCC. Urine AQP1 and PLIN2 concentrations were measured by sensitive and specific ELISA and Western blot procedures, respectively. AQP1 and PLIN2 were measured prospectively in a screening paradigm in an otherwise asymptomatic population. The absence or presence of a renal mass and of RCC, were verified by abdominal computed tomography (CT) and by post-nephrectomy pathologic diagnosis, respectively. Median urine AQP1 and PLIN2 concentrations in patients with known RCC were more than 12-fold higher (P<0.0001 each) than controls and the screening population. The area under the receiver operating characteristic curve for urine AQP1 and PLIN2 concentrations individually or in combination was ≥0.92, with ≥85% sensitivity and ≥87% specificity compared with control or screening patients. Three of the 720 screening patients had biomarker concentrations suggestive of RCC and were found to have an imaged renal mass by CT. Two patients, evaluated further, had RCC. These results demonstrate the clinical utility, specificity and sensitivity of urine AQP1 and PLIN2 to diagnose RCC. These novel tumor-specific proteins have high clinical validity and substantial potential as specific diagnostic and screening biomarkers for clear cell and papillary RCC, and in the differential diagnosis of imaged renal masses.