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Pinpointing new urinary biomarkers for bladder cancer detection and stage differentiation by label-free quantitative mass spectrometry
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Bladder cancer is the fourth most common neoplasia in more developed countries and the seventh worldwide, in the male gender. On cost per patient, it is also one of the most expensive malignancies at patient level, because current diagnostics, follow-up, and treatment are not cost-effective. Cystoscopy, the regular method to diagnose bladder cancer, is invasive, causes pain and it has a low sensibility. Furthermore, it is used to monitor recurrent urothelial carcinomas, contributing significantly to rise bladder cancer costs. Therefore, new non-invasive and more reliable methods of diagnosis and prognosis are needed.
Genetic mutations in bladder tumour cells, as well as tumour response from neighbouring cells and from the immune system, implicate protein expression and activation different from healthy people, therefore originating new features in the urine proteome. As urine is in direct contact with these tumour and urothelial cells, it is expected that changes in the bladder are reflected in the urine content. Therefore, the urinary proteome is an excellent biopsy for finding protein biomarkers of diagnosis and prognosis.
This work has the primary goal of finding a urine-based panel of biomarkers of diagnosis and staging for bladder cancer. The Hospital São José provided urine samples from patients who had Bladder Cancer as follows: (i) non-muscle invasive stages Ta and T1, and (ii) muscle invasive T2-T4 (T2+) and (iii) from other patients used as controls. So far, five groups were formed as indicated next: (a) bladder cancer-Ta; (b) T1; (c) T2+ (d) volunteers with no urothelial conditions and (e) volunteers presenting lower urinary tract symptoms.
The methodology selected to find the biomarkers was free-label quantification of peptides by High-Resolution Mass Spectrometry. To this end, the urine proteome was first separated and then digested using the Filter Aided Sample Preparation -FASP- method. The pools of peptides obtained were used to identify and quantify the proteins present in the urine samples. Then, using bioinformatics, data was interpreted, and two biomarker panels were obtained. The first panel consists of 35 proteins to diagnostic bladder cancer. The second panel consists of 76 proteins to stage bladder cancer.
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Biomarker Bladder Cancer Liquid Chromatography-Mass Spectrometry Proteomics Urine