Abstract
BackgroundUrothelial carcinoma of the bladder (UCB) is a common cancer of the urinary system. Despite substantial improvements in available treatment options, the survival outcome of patients with advanced UCB is unsatisfactory. Therefore, it is necessary to identify new prognostic biomarkers for monitoring and therapy guidance of UCB. In recent years, prostate-specific membrane antigen (PSMA) and CD248 have been identified promising candidate bio7markers.MethodsIn this study, we first examined PSMA and CD248 expression in tissues from 124 patients with UCB using immunohistochemical and immunofluorescent staining. We then analyzed the association between the expression of the two biomarkers and other clinicopathological features and prognosis. Finally, we performed bioinformatic analysis of CD248 and FOLH 1 (PSMA) using the TCGA-BLCA dataset to explore the underlying mechanism of PSMA and CD248 in the progression of UCB.ResultsAmong the 124 cases, PSMA and CD248 were confirmed to be expressed in tumor-associated vessels. Vascular PSMA and CD248 expression levels were associated significantly with several deteriorated clinicopathological features. Furthermore, using univariate and multivariate Cox analyses, high vascular PSMA and CD248 expression levels were observed to be associated significantly with poor prognosis in patients with UCB. As risk factors, both PSMA and CD248 expression showed good performance to predict prognosis. Furthermore, combining these vascular molecules with other clinical risk factors generated a risk score that could promote predictive performance. Bioinformatic analysis showed that both PSMA and CD248 might contribute to angiogenesis and promote further progression of UCB.ConclusionBoth PSMA and CD248 are specifically expressed in the tumor-associated vasculature of UCB. These two molecules might be used as novel prognostic biomarkers and vascular therapeutic targets for UCB.
Highlights
Urothelial carcinoma of the bladder (UCB), the commonest type of bladder cancer (BLCA), is the 10th most common cancer, with an estimated 549,000 new diagnoses and 200,000 deaths annually worldwide [1]
Apoptosis biomarkers, such as survivin, might be associated with outcomes in non−muscle −invasive bladder cancer (NMIBC) [9, 10]; survivin improved the accuracy of prediction of disease recurrence significantly in a subgroup of patients with pT2-3N0M0 disease [11], the evidence was insufficient for prognostic prediction in muscle-invasive bladder cancer (MIBC), and large prospective series are still lacking [12]
We found that prostate-specific membrane antigen (PSMA) and CD248 were both expressed in the vasculature in hepatocellular carcinoma (HCC), and vascular-expressed PSMA and CD248 might be used as prognostic markers and vascular therapeutic targets for HCC [30, 31]
Summary
Urothelial carcinoma of the bladder (UCB), the commonest type of bladder cancer (BLCA), is the 10th most common cancer, with an estimated 549,000 new diagnoses and 200,000 deaths annually worldwide [1]. A phase III trial designed to evaluate the benefit in patients with MIBC based on their p53 status for adjuvant cisplatin-based chemotherapy could not confirm the prognostic value of p53 alteration [8]. Apoptosis biomarkers, such as survivin, might be associated with outcomes in NMIBC [9, 10]; survivin improved the accuracy of prediction of disease recurrence significantly in a subgroup of patients with pT2-3N0M0 disease [11], the evidence was insufficient for prognostic prediction in MIBC, and large prospective series are still lacking [12]. Prostate-specific membrane antigen (PSMA) and CD248 have been identified promising candidate bio7markers
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