Expression and clinical significance of costimulatory molecule B7-H4 and programmed death ligand 1 in bladder cancer

Abstract

Objective To detect the expression of costimulatory molecules B7-H4 and programmed death ligand 1(PD-L1) in bladder cancer, and to explore the correlation between them and clinicopathological features of bladder cancer. Methods Immunohistochemical staining was used to detect the expression of B7-H4 and PD-L1 in 98 cases of bladder urothelial carcinoma, which were confirmed by pathology from August 2014 to December 2015 in our hospital. There were 23 females, aged 45-82 years, with an average age of 67.8 years. Among them, 42 cases of adjacent normal tissues were used as controls. The clinical stage, histological grade and recurrence of bladder cancer were collected, and the correlation between them was analyzed. Results The positive rates of B7-H4 and PD-L1 in bladder urothelial carcinoma were 54.1% (53/98) and 59.2% (58/98), respectively, and there was no expression in normal bladder tissues (P<0.05). The positive expression rate of B7-H4 in muscle invasive bladder cancer (MIBC) patients was higher than that in non-muscle invasive bladder cancer (NMIBC) [73.5% (25/34) vs. 43.8% (28/64), P=0.005]. The positive expression rate of B7-H4 in high-grade patients was higher than that of low-grade [70.0%(21/30) vs. 47.1%(32/68), P=0.036]. The expression rate of B7-H4 in high-risk group was higher than that of low-intermediate risk group [ 57.1%(20/35) vs. 27.6%(8/29), P=0.018]. The positive expression rate of PD-L1 in patients with MIBC was higher than that in NMIBC [79.4% (27/34) vs. 48.4% (31/64), P=0.003]. The PD-L1 expression rate of histological high-level group was higher than that of low-level group [ 73.3% (22/30) vs. 52.9% (36/68)], but the difference was not statistically significant (P=0.058). The PD-L1 expression rate in high-risk group was 68.6% (24/35), and also higher than low-middle group 24.1% (7/29) (P<0.05). There was a positive correlation between the expression of B7-H4 and PD-L1 in bladder urothelial carcinoma (r=0.318, P=0.002). The combined recurrence rate of the two groups was significantly higher than that of the negative expression of the two groups [66.7% ( 14/21) vs. 30.8% (8/26), P=0.014]. Conclusions The expression of B7-H4 and PD-L1 is up-regulated in bladder urothelial carcinoma, which is closely related to the clinical stage, histological grade, risk classification and recurrence of NMIBC. Key words: Costimulatory molecule; B7-H4; Programmed death-ligand 1; Bladder urothelial carcinoma