Abstract
Bladder urothelial carcinoma (BUC) is the most lethal malignancy of the urinary tract. Treatment for the disease highly depends on the invasiveness of cancer cells. Therefore, a predictive biomarker needs to be identified for invasive BUC. In this study, we employed proteomics methods on urine liquid-based cytology (LBC) samples and a BUC cell line library to determine a novel predictive biomarker for invasive BUC. Furthermore, an in vitro three-dimensional (3D) invasion study for biological significance and diagnostic validation through immunocytochemistry (ICC) were also performed. The proteomic analysis suggested moesin (MSN) as a potential biomarker to predict the invasiveness of BUC. The in vitro 3D invasion study showed that inhibition of MSN significantly decreased invasiveness in BUC cell lines. Further validation using ICC ultimately confirmed moesin (MSN) as a potential biomarker to predict the invasiveness of BUC (p = 0.023). In conclusion, we suggest moesin as a potential diagnostic marker for early detection of BUC with invasion in LBC and as a potential therapeutic target.
Highlights
Bladder urothelial carcinoma (BUC) is the most common and lethal malignancy of the urinary tract [1]
We explored proteome-based novel biomarkers to predict advanced tumor stage in voided urine cytology samples collected by liquid-based preparation and evaluated the predictive ability of moesin (MSN) in the context of bladder urothelial carcinoma (BUC) invasion through immunocytochemistry (ICC) validation in independent liquid-based cytology (LBC) cohorts
Multigroup tests with one-way ANOVA revealed 182 differentially expressed proteins (DEPs) among three cohorts based on pathologic T stage (Figure 1A, Table S2)
Summary
Bladder urothelial carcinoma (BUC) is the most common and lethal malignancy of the urinary tract [1]. Cancers 2020, 12, 1018 availability of different therapeutic approaches [2], which has prompted the identification of robust invasion-associated molecular characteristics of BUC [3,4]. We successfully conducted a proteomic study and validated a proteomebased novel diagnostic marker of BUC in liquid-based cytology (LBC) [11], which is the gold standard test for surveillance of urothelial carcinoma recurrence or progression [12,13]. Voided urine cytology used in this study is the standard non-invasive method for the detection of BUC by the assessment of morphologic changes of exfoliated urothelial cells in comparison to transurethral endoscopy which is more invasive and expensive. Recent cytologic slide-based ancillary tests showed anticipatory positive results by direct integration with cytomorphologic findings [14]
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