The specificity of urinary aquaporin 1 and perilipin 2 to screen for renal cell carcinoma
Jeremiah J Morrissey, Evan D Kharasch, Jeremiah J Morrissey, Evan D Kharasch
Abstract
Purpose: Renal cancer is frequently asymptomatic until late stages of the disease and it has a poor prognosis when not discovered early. AQP1 and PLIN2 are recently discovered, sensitive urine biomarkers of clear cell and papillary kidney cancer. We validated these biomarkers in a second cohort of patients and determined the effect of common kidney diseases on specificity.
Materials and methods: Urine samples were obtained from 36 patients with clear cell or papillary kidney cancer, 43 controls, 44 patients with documented urinary tract infection, 24 diagnosed with diabetic nephropathy and 18 diagnosed with glomerulonephritis. Urine levels of AQP1 and PLIN2 normalized to urine creatinine were determined by a sensitive, specific Western blot procedure.
Results: Compared with controls, urine AQP1 and PLIN2 levels in patients with kidney cancer were 23-fold and fourfold greater, respectively, and they decreased 83% to 84% after tumor excision. There was a linear correlation between urine AQP1 and PLIN2 levels, and tumor size (each p <0.001). Urine AQP1 and PLIN2 levels in patients with kidney cancer were 11 to 23-fold and 17 to 25-fold greater, respectively, than in patients with the common kidney diseases.
Conclusions: The ability of urine AQP1 and PLIN2 to identify patients with kidney cancer compared to controls was validated in a second cohort of patients. Common kidney diseases do not adversely increase urine AQP1 and PLIN2 levels or decrease their specificity to screen for renal cancer.
Trial registration: ClinicalTrials.gov NCT00851994.
Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3720141/bin/nihms-481106-f0001.jpg)
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3720141/bin/nihms-481106-f0002.jpg)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3720141/bin/nihms-481106-f0003.jpg)
Figure 2
Urinary biomarker concentrations as a…
Figure 2
Urinary biomarker concentrations as a function of tumor size. (A) AQP-1 Spearman correlation…
Figure 3
Pre- and post-nephrectomy urine AQP-1…
Figure 3
Pre- and post-nephrectomy urine AQP-1 and ADFP concentrations. Results are shown for only…
Figure 4
Urinary AQP-1 and ADFP levels…
Figure 4
Urinary AQP-1 and ADFP levels in patients with diabetic nephropathy (DN) (upper) or…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
- Evaluation of Urine Aquaporin-1 and Perilipin-2 Concentrations as Biomarkers to Screen for Renal Cell Carcinoma: A Prospective Cohort Study.Morrissey JJ, Mellnick VM, Luo J, Siegel MJ, Figenshau RS, Bhayani S, Kharasch ED. Morrissey JJ, et al. JAMA Oncol. 2015 May;1(2):204-12. doi: 10.1001/jamaoncol.2015.0213. JAMA Oncol. 2015. PMID: 26181025 Free PMC article.
- Urinary concentrations of aquaporin-1 and perilipin-2 in patients with renal cell carcinoma correlate with tumor size and stage but not grade.Morrissey JJ, Mobley J, Song J, Vetter J, Luo J, Bhayani S, Figenshau RS, Kharasch ED. Morrissey JJ, et al. Urology. 2014 Jan;83(1):256.e9-14. doi: 10.1016/j.urology.2013.09.026. Epub 2013 Nov 13. Urology. 2014. PMID: 24239027 Free PMC article.
- Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer.Morrissey JJ, Mobley J, Figenshau RS, Vetter J, Bhayani S, Kharasch ED. Morrissey JJ, et al. Mayo Clin Proc. 2015 Jan;90(1):35-42. doi: 10.1016/j.mayocp.2014.10.005. Mayo Clin Proc. 2015. PMID: 25572193 Free PMC article. Clinical Trial.
- Diagnostic and prognostic tissuemarkers in clear cell and papillary renal cell carcinoma.Kroeze SG, Bijenhof AM, Bosch JL, Jans JJ. Kroeze SG, et al. Cancer Biomark. 2010;7(6):261-8. doi: 10.3233/CBM-2010-0195. Cancer Biomark. 2010. PMID: 21694464 Review.
- Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer.Oto J, Plana E, Sánchez-González JV, García-Olaverri J, Fernández-Pardo Á, España F, Martínez-Sarmiento M, Vera-Donoso CD, Navarro S, Medina P. Oto J, et al. Curr Urol Rep. 2020 Mar 13;21(2):11. doi: 10.1007/s11934-020-0962-9. Curr Urol Rep. 2020. PMID: 32166474 Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Aquaporin 1 / urine*
- Carcinoma, Renal Cell / diagnosis*
- Carcinoma, Renal Cell / urine*
- Early Detection of Cancer / methods*
- Female
- Humans
- Kidney Neoplasms / diagnosis*
- Kidney Neoplasms / urine*
- Male
- Membrane Proteins / urine*
- Perilipin-2
- Sensitivity and Specificity
- Membrane Proteins
- PLIN2 protein, human
- Perilipin-2
- Aquaporin 1
- ClinicalTrials.gov/NCT00851994
- Full Text Sources
- Other Literature Sources
- Medical
- Research Materials
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3720141/bin/nihms-481106-f0004.jpg)
Figure 3
Pre- and post-nephrectomy urine AQP-1…
Figure 3
Pre- and post-nephrectomy urine AQP-1 and ADFP concentrations. Results are shown for only…
Figure 4
Urinary AQP-1 and ADFP levels…
Figure 4
Urinary AQP-1 and ADFP levels in patients with diabetic nephropathy (DN) (upper) or…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
- Evaluation of Urine Aquaporin-1 and Perilipin-2 Concentrations as Biomarkers to Screen for Renal Cell Carcinoma: A Prospective Cohort Study.Morrissey JJ, Mellnick VM, Luo J, Siegel MJ, Figenshau RS, Bhayani S, Kharasch ED. Morrissey JJ, et al. JAMA Oncol. 2015 May;1(2):204-12. doi: 10.1001/jamaoncol.2015.0213. JAMA Oncol. 2015. PMID: 26181025 Free PMC article.
- Urinary concentrations of aquaporin-1 and perilipin-2 in patients with renal cell carcinoma correlate with tumor size and stage but not grade.Morrissey JJ, Mobley J, Song J, Vetter J, Luo J, Bhayani S, Figenshau RS, Kharasch ED. Morrissey JJ, et al. Urology. 2014 Jan;83(1):256.e9-14. doi: 10.1016/j.urology.2013.09.026. Epub 2013 Nov 13. Urology. 2014. PMID: 24239027 Free PMC article.
- Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer.Morrissey JJ, Mobley J, Figenshau RS, Vetter J, Bhayani S, Kharasch ED. Morrissey JJ, et al. Mayo Clin Proc. 2015 Jan;90(1):35-42. doi: 10.1016/j.mayocp.2014.10.005. Mayo Clin Proc. 2015. PMID: 25572193 Free PMC article. Clinical Trial.
- Diagnostic and prognostic tissuemarkers in clear cell and papillary renal cell carcinoma.Kroeze SG, Bijenhof AM, Bosch JL, Jans JJ. Kroeze SG, et al. Cancer Biomark. 2010;7(6):261-8. doi: 10.3233/CBM-2010-0195. Cancer Biomark. 2010. PMID: 21694464 Review.
- Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer.Oto J, Plana E, Sánchez-González JV, García-Olaverri J, Fernández-Pardo Á, España F, Martínez-Sarmiento M, Vera-Donoso CD, Navarro S, Medina P. Oto J, et al. Curr Urol Rep. 2020 Mar 13;21(2):11. doi: 10.1007/s11934-020-0962-9. Curr Urol Rep. 2020. PMID: 32166474 Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Aquaporin 1 / urine*
- Carcinoma, Renal Cell / diagnosis*
- Carcinoma, Renal Cell / urine*
- Early Detection of Cancer / methods*
- Female
- Humans
- Kidney Neoplasms / diagnosis*
- Kidney Neoplasms / urine*
- Male
- Membrane Proteins / urine*
- Perilipin-2
- Sensitivity and Specificity
- Membrane Proteins
- PLIN2 protein, human
- Perilipin-2
- Aquaporin 1
- ClinicalTrials.gov/NCT00851994
- Full Text Sources
- Other Literature Sources
- Medical
- Research Materials
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3720141/bin/nihms-481106-f0005.jpg)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3720141/bin/nihms-481106-f0006.jpg)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3720141/bin/nihms-481106-f0007.jpg)
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
- Evaluation of Urine Aquaporin-1 and Perilipin-2 Concentrations as Biomarkers to Screen for Renal Cell Carcinoma: A Prospective Cohort Study.Morrissey JJ, Mellnick VM, Luo J, Siegel MJ, Figenshau RS, Bhayani S, Kharasch ED. Morrissey JJ, et al. JAMA Oncol. 2015 May;1(2):204-12. doi: 10.1001/jamaoncol.2015.0213. JAMA Oncol. 2015. PMID: 26181025 Free PMC article.
- Urinary concentrations of aquaporin-1 and perilipin-2 in patients with renal cell carcinoma correlate with tumor size and stage but not grade.Morrissey JJ, Mobley J, Song J, Vetter J, Luo J, Bhayani S, Figenshau RS, Kharasch ED. Morrissey JJ, et al. Urology. 2014 Jan;83(1):256.e9-14. doi: 10.1016/j.urology.2013.09.026. Epub 2013 Nov 13. Urology. 2014. PMID: 24239027 Free PMC article.
- Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer.Morrissey JJ, Mobley J, Figenshau RS, Vetter J, Bhayani S, Kharasch ED. Morrissey JJ, et al. Mayo Clin Proc. 2015 Jan;90(1):35-42. doi: 10.1016/j.mayocp.2014.10.005. Mayo Clin Proc. 2015. PMID: 25572193 Free PMC article. Clinical Trial.
- Diagnostic and prognostic tissuemarkers in clear cell and papillary renal cell carcinoma.Kroeze SG, Bijenhof AM, Bosch JL, Jans JJ. Kroeze SG, et al. Cancer Biomark. 2010;7(6):261-8. doi: 10.3233/CBM-2010-0195. Cancer Biomark. 2010. PMID: 21694464 Review.
- Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer.Oto J, Plana E, Sánchez-González JV, García-Olaverri J, Fernández-Pardo Á, España F, Martínez-Sarmiento M, Vera-Donoso CD, Navarro S, Medina P. Oto J, et al. Curr Urol Rep. 2020 Mar 13;21(2):11. doi: 10.1007/s11934-020-0962-9. Curr Urol Rep. 2020. PMID: 32166474 Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Aquaporin 1 / urine*
- Carcinoma, Renal Cell / diagnosis*
- Carcinoma, Renal Cell / urine*
- Early Detection of Cancer / methods*
- Female
- Humans
- Kidney Neoplasms / diagnosis*
- Kidney Neoplasms / urine*
- Male
- Membrane Proteins / urine*
- Perilipin-2
- Sensitivity and Specificity
- Membrane Proteins
- PLIN2 protein, human
- Perilipin-2
- Aquaporin 1
- ClinicalTrials.gov/NCT00851994
- Full Text Sources
- Other Literature Sources
- Medical
- Research Materials
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3720141/bin/nihms-481106-f0008.jpg)
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
- Evaluation of Urine Aquaporin-1 and Perilipin-2 Concentrations as Biomarkers to Screen for Renal Cell Carcinoma: A Prospective Cohort Study.Morrissey JJ, Mellnick VM, Luo J, Siegel MJ, Figenshau RS, Bhayani S, Kharasch ED. Morrissey JJ, et al. JAMA Oncol. 2015 May;1(2):204-12. doi: 10.1001/jamaoncol.2015.0213. JAMA Oncol. 2015. PMID: 26181025 Free PMC article.
- Urinary concentrations of aquaporin-1 and perilipin-2 in patients with renal cell carcinoma correlate with tumor size and stage but not grade.Morrissey JJ, Mobley J, Song J, Vetter J, Luo J, Bhayani S, Figenshau RS, Kharasch ED. Morrissey JJ, et al. Urology. 2014 Jan;83(1):256.e9-14. doi: 10.1016/j.urology.2013.09.026. Epub 2013 Nov 13. Urology. 2014. PMID: 24239027 Free PMC article.
- Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer.Morrissey JJ, Mobley J, Figenshau RS, Vetter J, Bhayani S, Kharasch ED. Morrissey JJ, et al. Mayo Clin Proc. 2015 Jan;90(1):35-42. doi: 10.1016/j.mayocp.2014.10.005. Mayo Clin Proc. 2015. PMID: 25572193 Free PMC article. Clinical Trial.
- Diagnostic and prognostic tissuemarkers in clear cell and papillary renal cell carcinoma.Kroeze SG, Bijenhof AM, Bosch JL, Jans JJ. Kroeze SG, et al. Cancer Biomark. 2010;7(6):261-8. doi: 10.3233/CBM-2010-0195. Cancer Biomark. 2010. PMID: 21694464 Review.
- Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer.Oto J, Plana E, Sánchez-González JV, García-Olaverri J, Fernández-Pardo Á, España F, Martínez-Sarmiento M, Vera-Donoso CD, Navarro S, Medina P. Oto J, et al. Curr Urol Rep. 2020 Mar 13;21(2):11. doi: 10.1007/s11934-020-0962-9. Curr Urol Rep. 2020. PMID: 32166474 Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Aquaporin 1 / urine*
- Carcinoma, Renal Cell / diagnosis*
- Carcinoma, Renal Cell / urine*
- Early Detection of Cancer / methods*
- Female
- Humans
- Kidney Neoplasms / diagnosis*
- Kidney Neoplasms / urine*
- Male
- Membrane Proteins / urine*
- Perilipin-2
- Sensitivity and Specificity
- Membrane Proteins
- PLIN2 protein, human
- Perilipin-2
- Aquaporin 1
- ClinicalTrials.gov/NCT00851994
- Full Text Sources
- Other Literature Sources
- Medical
- Research Materials
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3720141/bin/nihms-481106-f0009.jpg)
Figure 5
Receiver Operating Characteristic Curve analysis…
Figure 5
Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers…
- Evaluation of Urine Aquaporin-1 and Perilipin-2 Concentrations as Biomarkers to Screen for Renal Cell Carcinoma: A Prospective Cohort Study.Morrissey JJ, Mellnick VM, Luo J, Siegel MJ, Figenshau RS, Bhayani S, Kharasch ED. Morrissey JJ, et al. JAMA Oncol. 2015 May;1(2):204-12. doi: 10.1001/jamaoncol.2015.0213. JAMA Oncol. 2015. PMID: 26181025 Free PMC article.
- Urinary concentrations of aquaporin-1 and perilipin-2 in patients with renal cell carcinoma correlate with tumor size and stage but not grade.Morrissey JJ, Mobley J, Song J, Vetter J, Luo J, Bhayani S, Figenshau RS, Kharasch ED. Morrissey JJ, et al. Urology. 2014 Jan;83(1):256.e9-14. doi: 10.1016/j.urology.2013.09.026. Epub 2013 Nov 13. Urology. 2014. PMID: 24239027 Free PMC article.
- Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer.Morrissey JJ, Mobley J, Figenshau RS, Vetter J, Bhayani S, Kharasch ED. Morrissey JJ, et al. Mayo Clin Proc. 2015 Jan;90(1):35-42. doi: 10.1016/j.mayocp.2014.10.005. Mayo Clin Proc. 2015. PMID: 25572193 Free PMC article. Clinical Trial.
- Diagnostic and prognostic tissuemarkers in clear cell and papillary renal cell carcinoma.Kroeze SG, Bijenhof AM, Bosch JL, Jans JJ. Kroeze SG, et al. Cancer Biomark. 2010;7(6):261-8. doi: 10.3233/CBM-2010-0195. Cancer Biomark. 2010. PMID: 21694464 Review.
- Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer.Oto J, Plana E, Sánchez-González JV, García-Olaverri J, Fernández-Pardo Á, España F, Martínez-Sarmiento M, Vera-Donoso CD, Navarro S, Medina P. Oto J, et al. Curr Urol Rep. 2020 Mar 13;21(2):11. doi: 10.1007/s11934-020-0962-9. Curr Urol Rep. 2020. PMID: 32166474 Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Aquaporin 1 / urine*
- Carcinoma, Renal Cell / diagnosis*
- Carcinoma, Renal Cell / urine*
- Early Detection of Cancer / methods*
- Female
- Humans
- Kidney Neoplasms / diagnosis*
- Kidney Neoplasms / urine*
- Male
- Membrane Proteins / urine*
- Perilipin-2
- Sensitivity and Specificity
- Membrane Proteins
- PLIN2 protein, human
- Perilipin-2
- Aquaporin 1
- ClinicalTrials.gov/NCT00851994
- Full Text Sources
- Other Literature Sources
- Medical
- Research Materials
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3720141/bin/nihms-481106-f0010.jpg)
Source: PubMed