Abstract
Urothelial carcinoma of the urinary bladder (UCB) or bladder cancer remains a major health problem with high morbidity and mortality rates, especially in the western world. UCB is also associated with the highest cost per patient. In recent years numerous markers have been evaluated for suitability in UCB detection and surveillance. However, to date none of these markers can replace or even reduce the use of routine tools (cytology and cystoscopy). Our current study described UCB's extensive expression profile and highlighted the variations with normal bladder tissue. Our data revealed that JUP, PTGDR, KLRF1, MT-TC, and RNU6-135P are associated with prognosis in patients with UCB. The microarray expression data identified also S100A12, S100A8, and NAMPT as potential UCB biomarkers. Pathway analysis revealed that natural killer cell mediated cytotoxicity is the most involved pathway. Our analysis showed that S100A12 protein may be useful as a biomarker for early UCB detection. Plasma S100A12 has been observed in patients with UCB with an overall sensitivity of 90.5% and a specificity of 75%. S100A12 is highly expressed preferably in high-grade and high-stage UCB. Furthermore, using a panel of more than hundred urine samples, a prototype lateral flow test for the transcription factor Engrailed-2 (EN2) also showed reasonable sensitivity (85%) and specificity (71%). Such findings provide confidence to further improve and refine the EN2 rapid test for use in clinical practice. In conclusion, S100A12 and EN2 have shown potential value as biomarker candidates for UCB patients. These results can speed up the discovery of biomarkers, improving diagnostic accuracy and may help the management of UCB.
Highlights
Bladder cancer (- urothelial carcinoma of the urinary bladder, UCB) is the fourth and ninth most common cancer in men and women, respectively [1, 2]
We identified elevated expression of the human S100A12 as a bladder cancerenriched gene that is potentially a sensitive and specific diagnostic biomarker for UCB
Motivated by the fact that there is rapid growth in the demand for point-of-care tests based on lateral flow assays with high sensitivity, specificity and low cost, we developed a lateral flow rapid test for detection of EN2 in urine samples
Summary
Bladder cancer (- urothelial carcinoma of the urinary bladder, UCB) is the fourth and ninth most common cancer in men and women, respectively [1, 2]. There were several biomarkers used for diagnostic and monitoring purposes, but no marker has yet been shown to reduce the need for cystoscopy [6,7,8,9,10,11] This is especially problematic given the high recurrence rate, because of which lifelong surveillance is needed to detect any recurrence as early as possible [10]. Using a standard ELISA method, we have previously shown that urinary EN2 could be detected and used as a UCB diagnosis biomarker, even in the early and non-invasive stages of the disease [15]
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