Abstract
Bladder cancer is the 10th-most common cancer worldwide. The diagnosis and follow-up of patients require costly invasive methods and due to these expenses, bladder cancer continues to be one of the expensive malignancies. Early diagnosis is crucial in bladder cancer as it is in other cancers; therefore, non-invasive biomarkers for early diagnosis are very important. In this review, we aimed to focus on the most recent investigations on potential urinary micro RNA (miRNA) and protein biomarkers for bladder cancer diagnosis and their associated pathways. Studies performed by different groups were compiled and the biomarker properties of various proteins and miRNAs in the urine of bladder cancer patients were evaluated. Key studies were obtained by searching keywords “bladder cancer, urinary miRNA, urinary protein, urinary biomarker”. Targets and the pathways of the miRNAs and proteins were analyzed according to mirBase Catalogue and Panther Database. The major pathways that are targeted by aberrantly expressed miRNAs are Cholecystokinin receptor (CCKR), p53, Wnt signaling pathway, and feedback loops. We hereby conclude that urinary micro RNAs and proteins are promising candidates for bladder cancer diagnosis. It should be noted that urine collection, storage conditions, choice of fraction, and normalization strategies should be standardized.
Highlights
Cancer is the leading cause of death and a major health problem worldwide
Another multiplex panel analysis of proteins in urine samples of bladder cancer (BC), healthy controls and other samples with varying urological disorders revealed that urine concentrations of IL-8, matrix metalloproteinase (MMP)-9 and 10, PAI-1, ANG, and APOE were significantly increased in subjects with BC compared to healthy controls
Extracellular vesicle micro RNA (miRNA) were analyzed for recurrence, analysis show that miR-146a, miR-194, and let-7c levels are lower in recurrent low-grade cancer patients, while miR-30c-2 is up regulated in low grade relapsing cases [59]
Summary
Cancer is the leading cause of death and a major health problem worldwide. According to the Global Cancer Observatory (GLOBOCAN) database, bladder cancer (BC) is the 10th-most frequently detected cancer in both sexes and 9th-most lethal malignancy in men [1]. These are bladder tumor antigen (BTA) stat, BTA TRAK, nuclear matrix protein 22 (NMP22), NMP22 BladderCheck Test, uCyt, and UroVysion tests The sensitivity of these kits for bladder cancer diagnosis ranges from 57–82% to 74–88% and the sensitivity increases as the stage and degree of cancer increases. UroVysion bladder cancer kit detects chromosome 3, 7, 17 aneuploidies and loss of the 9p21 locus via fluorescence in situ hybridization (FISH) in urine specimens [9] These methods are either highly sensitive or specific, but never both. MiRNAs are small, 20–24 nucleotides long non-protein coding RNA gene products that mediate target messenger RNA (mRNA) degradation or translational repression and they can serve as oncogenes or tumor suppressors They can be extracted from a wide range of biological samples such as blood plasma, urine, feces, or biopsy specimens and are generally stable and resistant to various storage conditions. Identified targets and pathways were analyzed according to mirBase Catalogue and Panther Database
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