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Candidate urinary biomarker discovery in ureteropelvic junction obstruction: a proteomic approach
Hrair-George O Mesrobian1, Michael E Mitchell, William A See
1Department of Urology, Medical College and Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA. hmesrobi@mcw.edu
Insights
Urinary proteome analysis reveals distinct protein differences in infants with ureteropelvic junction obstruction. This finding may aid in classifying disease severity and selecting candidates for early surgery.
Area of Science:
- Biochemistry
- Pediatric Nephrology
- Proteomics
Background:
- Ureteropelvic junction obstruction (UPJO) progression is variable, with natural history unfolding over years.
- Urinary proteome analysis shows promise in differentiating UPJO from normal infants.
- Current diagnostic and prognostic methods for UPJO require refinement.
Purpose of the Study:
- To confirm findings on urinary proteome differences in UPJO using liquid chromatography/nano-spray mass spectrometry.
- To examine the urinary proteome in infants with unilateral grade IV UPJO compared to healthy controls.
- To identify potential urinary protein biomarkers for UPJO classification.
Main Methods:
- Urine specimens collected from 21 healthy infants and 25 infants with grade IV unilateral UPJO.
- Liquid chromatography/tandem mass spectrometry (LC-MS/MS) used for proteomic analysis.
- Data normalization and annotation performed using the IPA knowledge platform.
Main Results:
- Significant differences in protein abundance observed between UPJO infants and controls at 1-6 months (31 proteins) and 7-12 months (18 proteins).
- Identified proteins clustered into major functional networks.
- Previously reported UPJO biomarkers were detected, except for transforming growth factor-beta1.
Conclusions:
- Confirms significant urinary proteome differences in unilateral UPJO compared to healthy infants.
- Provides new data on specific protein and peptide abundance in UPJO.
- Suggests potential for improved disease subgroup classification and early surgical candidate selection based on urinary biomarkers.
Purpose:
Ureteropelvic junction obstruction may either worsen and require surgery, improve or remain stable. It may take upward of 3 years for the natural history to unfold. Urinary proteome analysis using capillary electrophoresis mass spectrometry has been shown to differentiate between normal infants and those with ureteropelvic junction obstruction. We sought to confirm these findings using liquid chromatography/nano-spray mass spectrometry to examine the urinary proteome in patients with unilateral grade IV ureteropelvic junction obstruction compared to age matched healthy infants.
Materials And Methods:
Urine specimens were obtained from 21 healthy infants with normal maternal/fetal ultrasound and 25 infants with grade IV unilateral ureteropelvic junction obstruction. Specimens were prepared using standard methods and subjected to liquid chromatography/tandem mass spectrometry analysis. Normalized data were annotated using the IPA(R) knowledge platform.
Results:
There were 31 proteins significantly different in their level of abundance at 1 to 6 months, and 18 at 7 to 12 months compared to age matched controls. These proteins clustered into major functional networks. All of the biomarkers previously reported in clinical studies of ureteropelvic junction obstruction were observed with the notable exception of transforming growth factor-beta1.
Conclusions:
These results confirm the presence of significant differences in the urinary proteome in unilateral ureteropelvic junction obstruction compared to age matched normal individuals. This study adds new information about levels of abundance of specific proteins and peptides in ureteropelvic junction obstruction, which may allow for better classification of disease subgroups and help to establish improved indications for the early selection of surgical candidates based on urinary protein biomarkers.
