Abstract
Bladder cancer biomarkers currently approved by the Food and Drug Administration are insufficiently reliable for use in non-invasive clinical diagnosis. Verification/validation of numerous biomarker candidates for BC detection is a crucial bottleneck for novel biomarker development. A multiplexed liquid chromatography multiple-reaction-monitoring mass spectrometry assay of 122 proteins, including 118 up-regulated tissue proteins, two known bladder cancer biomarkers and two housekeeping gene products, was successfully established for protein quantification in clinical urine specimens. Quantification of 122 proteins was performed on a large cohort of urine specimens representing a variety of conditions, including 142 hernia, 126 bladder cancer, 67 hematuria, and 59 urinary tract infection samples. ANXA3 (annexin A3) and HSPE1 (heat shock protein family E member 1), which showed the highest detection frequency in bladder cancer samples, were selected for further validation. Western blotting showed that urinary ANXA3 and HSPE1 protein levels were higher in bladder cancer samples than in hernia samples, and enzyme-linked immunosorbent assays confirmed a higher urinary concentration of HSPE1 in bladder cancer than in hernia, hematuria and urinary tract infection. Immunohistochemical analyses showed significantly elevated levels of HSPE1 in tumor cells compared with non-cancerous bladder epithelial cells, suggesting that HSPE1 could be a useful tumor tissue marker for the specific detection of bladder cancer. Collectively, our findings provide valuable information for future validation of potential biomarkers for bladder cancer diagnosis.
Highlights
Bladder cancer (BC) is one of the most common urinary tract carcinomas
Western blotting showed that urinary ANXA3 and HSPE1 protein levels were higher in bladder cancer samples than in hernia samples, and enzyme-linked immunosorbent assays confirmed a higher urinary concentration of HSPE1 in bladder cancer than in hernia, hematuria and urinary tract infection
These results indicate that urinary HSPE1 is a potential candidate for the non-invasive early detection of BC and can be used to discriminate BC from hernia, hematuria, and Urinary tract infection (UTI)
Summary
Bladder cancer (BC) is one of the most common urinary tract carcinomas. On the basis of global cancer statistics, it is estimated that BC accounted for 330,400 new cases of cancer and 123,100 cancer-related deaths worldwide during 2012, making it the sixth-most common cancer and the ninth-leading cause of death [1]. More than 90% of BC patients are diagnosed with transitional cell carcinoma, 5% with squamous cell carcinoma, and less than 2% with adenocarcinoma [3]. Of diagnosed BC cases, approximately 70%–80% will present with non-muscle–invasive carcinoma, 50%–70% will recur, and 10%–30% will progress to muscle-invasive disease [4]. Recurrence takes place within 5 years, and patients with higher-grade lesions are at greater risk for tumor progression [5].
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