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Background Data mining from a published transcriptome of urinary bladder urothelial carcinomas (GSE32894), PTP4A3 was identified as the most significantly upregulated gene among those related to prenylated protein tyrosine phosphatase activity (GO: 0004727). We therefore analysed PTP4A3 transcript and protein expression and their clinicopathological and prognostic significance in our well-characterised cohort of urothelial carcinomas. Methods PTP4A3 transcript level was assessed in 23 samples of urothelial carcinoma of the urinary bladder with laser capture microdissection coupled with real-time qRT-PCR. PTP4A3 protein expression was determined by immunohistochemistry and evaluated by using H-score in 296 urinary bladder urothelial carcinomas and 340 upper urinary tract urothelial carcinomas, respectively. Both transcript and protein expression statuses were further correlated with clinicopathological features and protein expression was tested for disease-specific survival (DSS) and metastasis-free survival (MeFS). Findings PTP4A3 transcripts were markedly upregulated in deeply invasive urothelial carcinomas (p Interpretation PTP4A3 overexpression is an independent prognosticator for urothelial carcinoma, suggesting its potential prognostic and therapeutic value in urothelial carcinoma.

Background Through data mining of a published transcriptomic database of urothelial carcinomas of the urinary bladder (GSE32894), colony stimulating factor 2 (CSF2) was identified as the most significant gene showing stepwise upregulation related to positive regulation of tyrosine phosphorylation of STAT5 (GO:0042523). We therefore analysed CSF2 transcript and protein expression and their association with clinicopathological factors and survival in our well-characterised cohort of urothelial carcinomas. Methods Laser capture microdissection coupled with real-time qRT-PCR was used to detect CSF2 transcript level in 24 urothelial carcinomas of the urinary bladder and six non-tumour urothelium samples. Immunohistochemistry evaluated by using H-score was used to determine CSF2 protein expression in 296 urothelial carcinomas of the urinary bladder and 340 urothelial carcinomas of the upper urinary tract. Protein expression was correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). Findings CSF2 transcripts were detected exclusively in tumour lesions (p = 0.010) with stepwise upregulation. CSF2 protein overexpression was significantly associated with advanced pT status (urothelial carcinomas of the upper urinary tract, p = 0.011; urothelial carcinomas of the urinary bladder, p Interpretation CSF2 overexpression is associated with advanced clinical features for both patients with urothelial carcinomas of the upper urinary tract and urothelial carcinomas of the urinary bladder, suggesting it may serve as a potential prognostic and a novel therapeutic target of urothelial carcinoma.

Background Alpha-methylacyl CoA racemase (AMACR) is essential for catabolism of branched-chain fatty acids, allowing their subsequent β -oxidation to generate energy. However, its significance has not been assessed in urothelial carcinoma. We therefore analysed the clinicopathological and biological significance of AMACR expression in urothelial carcinoma. Methods Laser capture microdissection coupled with real-time qRT-PCR was used to detect AMACR transcript level in 22 urothelial carcinomas of the urinary bladder. Immunohistochemistry evaluated by using H-score was used to determine AMACR protein expression in 295 urothelial carcinomas of the urinary bladder and 340 urothelial carcinomas of the upper urinary tract. mRNA and protein expression were correlated with clinicopathological features. AMACR protein expression was further evaluated for associations with disease-specific survival (DSS) and metastasis-free survival (MeFS). In vitro, AMACR overexpressing urothelial carcinoma cell lines (BFTC905 and RTCC-1) were evaluated for its biological function using RNA interference. Findings Increments of AMACR transcript level was associated with higher pT status ( p = 0.017). AMACR protein overexpression was significantly associated with advanced pT status (both p p ⩽ 0.001), high histological grade (both p ⩽ 0.001), vascular invasion (urothelial carcinomas of the upper urinary tract, p p = 0.003), frequent mitoses (urothelial carcinomas of the upper urinary tract, p = 0.007; urothelial carcinomas of the urinary bladder, p p = 0.025; urothelial carcinomas of the urinary bladder, p = 0.001) and MeFS (urothelial carcinomas of the upper urinary tract, p = 0.028; urothelial carcinomas of the urinary bladder, p = 0.019) in multivariate analysis. In both urothelial carcinoma cell lines, stable AMACR knockdown resulted in impaired cell proliferation, as well as migration/invasion capabilities. Interpretation AMACR overexpression is associated with advanced clinical features for patients with urothelial carcinoma and may serve as a potential prognostic biomarker and a novel therapeutic target.

Background Through data mining from a published transcriptomic database of urinary bladder urothelial carcinomas (GSE32894), MMP11 was identified as the most significant gene showing stepwise upregulation among those associated with the regulation of metalloendopeptidase activity. We therefore analysed MMP11 protein expression and its association with clinicopathological factors and survival in our well-characterised cohort of urothelial cancers. Methods Immunohistochemistry evaluated by using H-score was used to determine MMP11 protein expression in 295 urothelial carcinomas of the urinary bladder and 340 urothelial carcinomas of the upper urinary tract, respectively. The medical records of these patients were reviewed retrospectively. The MMP11 expression status was further correlated with clinicopathological features as well as disease-specific survival (DSS) and metastasis-free survival (MeFS). Univariate and multivariate statistical analyses were performed to evaluate the prognostic predictors. Findings MMP11 protein overexpression was significantly associated with advanced pT status (upper urinary tract, p Interpretation MMP11 overexpression is associated with more aggressive tumour phenotype and poor prognosis for patients with urothelial carcinomas of the upper urinary tract and urinary bladder, suggesting it may serve as a potential prognostic and a novel therapeutic target of urothelial carcinoma.