Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China; Department of Anesthesiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Department of Mechanical Engineering and Materials Science, Institute of Materials Science and Engineering, Washington University in St. Louis, St Louis, Missouri, USA.
Kidney Int. 2019 Dec;96(6):1417-1421. doi: 10.1016/j.kint.2019.08.020. Epub 2019 Sep 3.
Renal cell carcinoma (RCC) has poor survival prognosis because it is asymptomatic at an early, more curative stage. Recently, urine perilipin-2 (PLIN-2) was demonstrated to be a sensitive and specific biomarker for the noninvasive, early detection of RCC and an indispensable indicator to distinguish cancer from a benign renal mass. However, current Western blot or ELISA PLIN-2 assays are complicated, expensive, time-consuming or insensitive, making them unsuitable for routine analysis in clinical settings. Here we developed a plasmonic biosensor based on the high refractive index sensitivity of gold nanorattles for the rapid detection of PLIN-2 in patient urine. The paper-based plasmonic assay is highly sensitive and has a dynamic range of 50 pg/ml to 5 μg/ml PLIN-2. The assay is not compromised by variations in urine pH or high concentrations of interfering proteins such as albumin and hemoglobin, making it an excellent candidate for routine clinical applications. The urine PLIN-2 assay readily distinguished patients with pathologically proven clear cell carcinomas of various size, stage and grade (55.9 [39.5, 75.8] ng/ml, median [1st and 3rd quartile]) from age-matched controls (0.3 [0.3, 0.5] ng/ml), patients with bladder cancer (0.5 [0.4, 0.6] ng/ml) and patients with diabetic nephropathy (0.6 [0.4, 0.7] ng/ml). Urine PLIN-2 concentrations were roughly proportional to tumor size (Pearson coefficient 0.59). Thus, this cost-effective and label-free method represents a novel approach to conduct a non-invasive population screen or rapid differential diagnosis of imaged renal masses, significantly facilitating the early detection and diagnosis of RCC.
肾细胞癌（RCC）的预后较差，因为在早期更具治疗意义的阶段，它无症状。最近，尿液 perilipin-2（PLIN-2）被证明是一种敏感且特异的生物标志物，可用于非侵入性、早期检测 RCC，也是区分癌症和良性肾肿瘤所必需的指标。然而，目前 Western blot 或 ELISA PLIN-2 检测法较为复杂、昂贵、耗时或不灵敏，不适合在临床环境中进行常规分析。在此，我们开发了一种基于金纳米棒高折射率灵敏度的等离子体生物传感器，用于快速检测患者尿液中的 PLIN-2。基于纸的等离子体检测法具有高灵敏度，PLIN-2 的动态检测范围为 50pg/ml 至 5μg/ml。该检测法不受尿液 pH 值变化或白蛋白和血红蛋白等高浓度干扰蛋白的影响，是常规临床应用的优秀候选方法。尿液 PLIN-2 检测法可轻松区分病理证实的不同大小、分期和分级的透明细胞癌患者（55.9[39.5,75.8]ng/ml，中位数[1 四分位距，3 四分位距]）与年龄匹配的对照组（0.3[0.3,0.5]ng/ml）、膀胱癌患者（0.5[0.4,0.6]ng/ml）和糖尿病肾病患者（0.6[0.4,0.7]ng/ml）。尿液 PLIN-2 浓度与肿瘤大小大致呈正比（皮尔逊相关系数 0.59）。因此，这种具有成本效益且无需标记的方法代表了一种新的方法，可以进行非侵入性人群筛查或对成像肾肿块进行快速鉴别诊断，极大地促进了 RCC 的早期检测和诊断。
