Aquaporin-1 protein levels elevated in fresh urine of renal cell carcinoma patients: potential use for screening and classification of incidental renal lesions.

Shilpa Sreedharan,Kenneth Ogan,David L Roberts,Fei Lian,Viraj A Master,Rebecca S Arnold,John A Petros,John G Pattaras

doi:10.1155/2014/135649

Abstract

Introduction and Objectives. There are over 65,000 new cases of renal cell carcinoma (RCC) each year, yet there is no effective clinical screening test for RCC. A single report claimed no overlap between urine levels of aquaporin-1 (AQP1) in patients with and without RCC (Mayo Clin Proc. 85:413, 2010). Here, we used archived and fresh RCC patient urine to validate this report. Methods. Archived RCC, fresh prenephrectomy RCC, and non-RCC negative control urines were processed for Western blot analysis. Urinary creatinine concentrations were quantified by the Jaffe reaction (Nephron 16:31, 1976). Precipitated protein was dissolved in 1x SDS for a final concentration of 2 μg/µL creatinine. Results. Negative control and archived RCC patient urine failed to show any AQP1 protein by Western blot analysis. Fresh RCC patient urine is robustly positive for AQP1. There was no signal overlap between fresh RCC and negative control, making differentiation straightforward. Conclusions. Our data confirms that fresh urine of patients with RCC contains easily detectable AQP1 protein. However, archival specimens showed an absence of detectable AQP1 indistinguishable from negative control. These findings suggest that a clinically applicable diagnostic test for AQP1 in fresh urine may be useful for detecting RCC.

Highlights

Introduction and ObjectivesThere are over 65,000 new cases of renal cell carcinoma (RCC) each year, yet there is no effective clinical screening test for RCC
Over 65,000 individuals are diagnosed with renal cell carcinoma (RCC) in the United States each year, and over 13,500 of these cases are fatal [1]
RCC is resistant to chemotherapy and metastatic disease has a five-year survival rate of 5% or less [6]

Summary

Introduction

Introduction and ObjectivesThere are over 65,000 new cases of renal cell carcinoma (RCC) each year, yet there is no effective clinical screening test for RCC. Negative control and archived RCC patient urine failed to show any AQP1 protein by Western blot analysis. Archival specimens showed an absence of detectable AQP1 indistinguishable from negative control These findings suggest that a clinically applicable diagnostic test for AQP1 in fresh urine may be useful for detecting RCC. Over 65,000 individuals are diagnosed with renal cell carcinoma (RCC) in the United States each year, and over 13,500 of these cases are fatal [1]. Both the incidence and detection rate of RCC have been increasing steadily since the 1970s [2]. The lack of a diagnostic biomarker for RCC presents a significant drawback in screening and clinical evaluation of incidentally discovered renal masses at a time amenable to surgical cure

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Conclusion