TY - JOUR
T1 - Bioplasmonic paper–based assay for perilipin-2 non-invasively detects renal cancer
AU - Hu, Rong
AU - Gupta, Rohit
AU - Wang, Zheyu
AU - Wang, Congzhou
AU - Sun, Hongcheng
AU - Singamaneni, Srikanth
AU - Kharasch, Evan D.
AU - Morrissey, Jeremiah J.
N1 - Funding Information:
The work was supported by grants 3706 and 3952 from The Foundation for Barnes-Jewish Hospital; by National Institutes of Health grants CA141521 to JJM and DK100759 to SS; and a grant from the National Natural Science Foundation of China 8130655 to RH. PLIN-2, also known as ADFP, is subject in part to patents US9091690, US9494590, EP2433137, and EP2863225 to EDK and JJM and patent US9410949B2 to EDK, JJM, and SS. To date, there are no financial interests related to these patents. The authors would like to thank Clinical Coordinators Marilee Fisher, Cynthia Tang, and Aaron Steinberg for consenting patients and biobanking patient urine samples and Ross Rosen (student Department of Energy, Environmental, and Chemical Engineering) for help with the patient PLIN-2 measurements.
Funding Information:
The work was supported by grants 3706 and 3952 from The Foundation for Barnes-Jewish Hospital; by National Institutes of Health grants CA141521 to JJM and DK100759 to SS; and a grant from the National Natural Science Foundation of China 8130655 to RH. PLIN-2, also known as ADFP, is subject in part to patents US9091690, US9494590, EP2433137, and EP2863225 to EDK and JJM and patent US9410949B2 to EDK, JJM, and SS. To date, there are no financial interests related to these patents. The authors would like to thank Clinical Coordinators Marilee Fisher, Cynthia Tang, and Aaron Steinberg for consenting patients and biobanking patient urine samples and Ross Rosen (student Department of Energy, Environmental, and Chemical Engineering) for help with the patient PLIN-2 measurements.
Publisher Copyright:
© 2019 International Society of Nephrology
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - bioplasmonic assay
KW - cancer biomarkers
KW - cancer diagnostics
KW - renal cancer
UR - http://www.scopus.com/inward/record.url?scp=85074390747&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2019.08.020
DO - 10.1016/j.kint.2019.08.020
M3 - Article
C2 - 31668633
AN - SCOPUS:85074390747
SN - 0085-2538
VL - 96
SP - 1417
EP - 1421
JO - Kidney International
JF - Kidney International
IS - 6
ER -