Discovery of Bladder Cancer Biomarkers in Paired Pre- and Postoperative Urine Samples.

BACKGROUND:Bladder cancer (BC), a common cancer of the urinary system, has a low mortality but an extremely high recurrence rate. Patients who have undergone initial surgical treatment often undergo frequent prognostic examinations with a substantial burden of discomfort and costs. Urine samples can reflect early disease processes in the urinary system and may be an excellent source of biomarkers.METHODS:In the present study, we used the liquid chromatography with tandem mass spectrometry (LC-MS/MS) to perform proteomic analysis of pre- and postoperative urine samples from patients with stage III BC to identify biomarkers of cancer prognosis. Candidate biomarkers from proteomic analysis were simultaneously validated using western blotting in an independent cohort and immunohistochemical (IHC) staining, combined with gene expression data of BC samples in The Cancer Genome Atlas (TCGA).RESULTS:The comparison of pre- and postoperative urine samples from the same patients led to the discovery of several significantly differentially expressed proteins, whose functions could be closely related to the occurrence and development of BC. We confirmed a representative group of candidate biomarker molecules, such as cadherin-related family member 2 (CDHR2), heat shock protein beta-1 (HSP27), and heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1).CONCLUSIONS:The candidate biomarker molecules can distinguish between pre- and postoperative urine samples, and alterations in their expression levels are significantly associated with recurrence rates in patients with BC. Therefore, these molecules may become useful biomarkers for the monitoring and prognosis of BC.