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.
Kidney international. 2019 Sep 03 [Epub]
Rong Hu, Rohit Gupta, Zheyu Wang, Congzhou Wang, Hongcheng Sun, Srikanth Singamaneni, Evan D Kharasch, Jeremiah J Morrissey
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., Nanoscience and Nanoengineering Program, South Dakota School of Mines and Technology, Rapid City, South Dakota, USA., Department of Mechanical Engineering and Materials Science, Institute of Materials Science and Engineering, Washington University in St. Louis, St Louis, Missouri, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, USA., Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USA., Department of Anesthesiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, USA. Electronic address: .