Prognostic Implication of Urothelial Stem Cell Markers Differs According to Primary Tumour Location in Non-Muscle-Invasive Bladder Cancer

Abstract

Background/Aims: This study aimed to validate the value of urothelial stem cell (USC) markers ΔNp63, integrin β4, CD47, and CD44v6 in predicting the prognosis of non-muscle invasive bladder cancer (NMIBC) located in different anatomic regions of bladder. Methods: The study reviewed the clinicopathologic data of 169 patients with NMIBC. Using real-time PCR and immunohistochemistry, the expression of ΔNp63, integrin β4, CD47, and CD44v6 in archived specimens of patients with NMIBC were validated. Kaplan–Meier analysis and Cox proportional hazards model were used to assess the prognostic impact of USC markers for recurrent-free survival (RFS). Results: The Real-time PCR data showed that the expression of USC markers were higher in tumors located in the trigone and posterior wall than that in other regions of bladder (P< 0.05). Statistical analysis showed that high expression of ΔNp63 was correlated with tumor stage (P=0.023) and tumor size (P=0.001), that high expression of integrin β4 was correlated with tumor stage (P=0.026), tumor grade (P=0.005) and tumor size (P=0.003), and that high integrin β4, CD47, and CD44v6 expression were significantly associated with tumor recurrence (P=0.032, P=0.010, and P=0.043, respectively). Moreover, high expression of ΔNp63 and integrin β4 was correlated with poor RFS in patients with tumors located in the trigone (P=0.025 and P=0.023, respectively). High expression of integrin β4, CD47, and CD44v6 was correlated with poor RFS in patients with tumors in the posterior wall (P=0.017, P=0.033 and P=0.047, respectively). High expression of integrin β4 and CD47 was correlated with poor RFS in patients with tumors in the trigone/posterior wall area (P=0.002 and P=0.005, respectively). Conclusion: Our results suggest that USC markers are linked with poor prognosis of NMIBC patients, especially in patients with tumors in the trigone and posterior wall.

Vitamin A Rich Diet Diminishes Early Urothelial Carcinogenesis by Altering Retinoic Acid Signaling

“…On the other hand, comparing the BBN + VitA group to the NT group, no significant downregulation was detected (except for Foxa1) (Table 1, Figure 5). The expression of Wnt target Sox9 was upregulated in early bladder carcinogenesis (BBN group compared to NT group), which is in accordance with studies showing upregulation of Sox9 in bladder cancer [51,52]. Surprisingly, Wnt5a was downregulated in the BBN group compared to the NT group.…”

CD47 is highly expressed in gliomas and targeting CD47 is a promising therapeutic strategy

“…19 Until now, although the role of CD47 has been studied in a number of cancers, the association between clinicopathological stage and CD47 expression has not been examined in gliomas. [20][21][22][23][24] In the present study, we collected all gilomas specimes in our hospital between 2013 and 2018 year, but 75% gilomas patients in our hospital were with grade II or III clinical diagnoses and relatively few cases were with grade I and grade IV clinical diagnoses. It is a limitation to explore the association between clinicopathological stage and CD47 expression, but the results indicated the expression of CD47 increased with increasing grade of glioma, and to some extent they were associated with clinicopathological stage.…”

TP63 isoform expression is linked with distinct clinical outcomes in cancer

“…Genome-wide association studies (GWAS) have found that bladder cancer risk is associated with a sequence variant of an enhancer specifically controlling DNp63 expression [12,13]. In contrast, DNp63 in NMIBC did not correlate with tumor risk of relapse [45] and was associated with reduced risk of invasive progression in T1 bladder tumors [8]. Further, high expression of DNp63 (p40) protein was associated with reduced patient survival in MIBC patients [46].…”