Exploring the Biomarkers Panel for Pediatric Patients with Different Vesicoureteral Reflux Degree by Urine Proteomics

Developing an effective non-invasive diagnostic scheme for early diagnosis and clinical management for pediatric urological/nephrological disease, such as vesicoureteral reflux (VUR), remains a challenging task. Urine biomarker is considered to be of potential for such a non-invasive diagnostic application since urine sample is stable and contains vast amount of proteins that reflect the physiological functions as well as pathological variations in kidney and urinary tract. Nevertheless, past findings on single biomarker studies are rarely applicable effectively in clinical setting, partly due to the lack of specificity and, if specific enough, only applicable in the disease acute stage. Henceforth, to develop a combination of urine biomarkers (i.e. biomarker panel), qualitatively and quantitatively, is considered to be a sounding alternative. Such a urine biomarker panel has been recently applied on different renal diseases, including cancer, due to the fast technological progress in urinary proteomics.For diagnosing pediatric patients with VUR, the radioactive and invasive voiding cystourethrography (VCUG) remains to be the gold standard. Furthermore, the patients need to have regular follow-ups with repetitive radioactive invasive imaging to monitor the disease progression if the initial clinical symptoms were not severe enough. Henceforth, developing a non-invasive diagnosing scheme becomes desirable for the clinical management in pediatric patients with VUR.This proposal is aimed to develop the urinary proteomics platform for an effective non-invasive diagnosis scheme for pediatric patients with VUR, using the 4-plex iTRAQ-LC/MS/MS and MRM-MS techniques developed at Proteomics Core Lab in Chang Gung University. These techniques have been demonstrated in the urinary proteomics study for bladder cancer. Patients diagnosed with VUR are divided into three subgroups, namely: VUR Grade I-II, Grade III, and Grade IV-V that is often recommended receiving surgical treatment. Age-matched normal controls (i.e. no proteinuria; normal renal ultrasound and normal renal function) are also included. In addition, patients and normal control had acute infectious diseases, UTIs as well as other renal diseases other than hydronephrosis, such as glomerulonephritis or nephrotic syndrome, are excluded from this study. Through the discovery and subsequent validation experiments for the protein biomarker candidates, an integration of multiple biomarkers as a “biomarker panel” will be determined. This biomarker panel does not only serve as the basis for diagnosis scheme but also to enhance our understanding in the pathological variations among the patients with VUR at different clinical severity.

Project ID:PC10907-1002
External Project ID:MOST109-2314-B182-039