Abstract
Non-muscle-invasive bladder cancer (NMIBC) is one of the most common malignant tumors in the urological system with a high risk of recurrence, and effective non-invasive biomarkers for NMIBC relapse are still needed. The human urinary proteome can reflect the status of the microenvironment of the urinary system and is an ideal source for clinical diagnosis of urinary system diseases. Our previous work used proteomics to identify 1643 high-confidence urinary proteins in the urine from a healthy population. Here, we used bioinformatics to construct a cancer-associated protein-protein interaction (PPI) network comprising 16 high-abundance urinary proteins based on the urinary proteome database. As a result, platelet-derived growth factor receptor beta (PDGFRB) was selected for further validation as a candidate biomarker for NMIBC diagnosis and prognosis. Although the levels of urinary PDGFRB showed no significant difference between patients pre- and post-surgery (n = 185, P>0.05), over 3 years of follow-up, urinary PDGFRB was shown to be significantly higher in relapsed patients (n = 68) than in relapse-free patients (n = 117, P<0.001). The levels of urinary PDGFRB were significantly correlated with the risk of 3-year recurrence of NMIBC, and these levels improved the accuracy of a NMIBC recurrence risk prediction model that included age, tumor size, and tumor number (area under the curve, 0.862; 95% CI, 0.809 to 0.914) compared to PDGFR alone. Therefore, we surmise that urinary PDGFRB could serve as a non-invasive biomarker for predicting NMIBC recurrence.
Highlights
Bladder cancer is the seventh most prevalent cancer worldwide, and approximately 80% of cases are non-muscle-invasive bladder cancer (NMIBC), while the remaining 20% are muscle-invasive bladder cancer (MIBC)[1,2,3]
We sought to screen potential biomarkers for NMIBC diagnosis and prognosis by constructing a cancer-associated protein-protein interaction (PPI) network based on the healthy human urinary proteome, and we revealed that plateletderived growth factor receptor beta (PDGFRB) could serve as a prognostic biomarker for NMIBC recurrence
It was further observed that EGF and CDH1 in the PPI network were annotated as being bladder cancer-associated proteins, and both receptor FGFR2 and PDGFRB could interact with EGF (Table 3)
Summary
Bladder cancer is the seventh most prevalent cancer worldwide, and approximately 80% of cases are non-muscle-invasive bladder cancer (NMIBC), while the remaining 20% are muscle-invasive bladder cancer (MIBC)[1,2,3]. Current clinical and conventional histopathological parameters such as tumor stage, grade and size of tumors, are well studied in terms of providing prognostic information regarding progression to muscle invasion and recurrence. None of these factors have proven to be sufficient to predict the diverse behavior of NMIBC. Biomarkers for NMIBC recurrence, which are non-invasive, are urgently required for clinical treatment
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