B7-H3 promotes malignant progression of muscle-invasive bladder cancer

Abstract

The objective of the present study was to investigate the expression of B7 homologue 3 (B7-H3) in muscle-invasive bladder cancer (MIBC) tissues, evaluate its correlation with patient clinicopathological characteristics, and to explore the effect of B7-H3 on MIBC cells. B7-H3 expression levels in tumor tissues from 115 patients undergoing radical cystectomy for MIBC were detected by immunohistochemical staining, followed by analysis of the association with clinicopathological characteristics and survival. A B7-H3-silenced cell line was established by RNA interference (RNAi). Alterations in cell proliferation, cell cycle, migration and invasion were analyzed in vitro. The proteins associated with cancer cell behavior were detected by western blot analysis. In addition, we utilized a xenograft tumor assay in nude mice to test the inhibitory effect of B7-H3 shRNA on MIBC in vivo. The results revealed that, among the 115 patients, the B7-H3 expression level was significantly associated with an increased incidence of distant metastasis (P=0.014) and vascular invasion (P=0.031), whereas it was not statistically associated with sex, age, pathologic grade, tumor stage, recurrence and lymphatic metastasis. Overall survival (OS) and progression-free survival (PFS) were significantly worse for patients with high B7-H3 expression (P<0.001 and P<0.001, respectively) among the 115 MIBC patients. Suppression of B7-H3 significantly inhibited the proliferation, caused G2 phase arrest, as well as declined migration and invasion abilities in vitro. The protein expression of Ki67, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP2) and MMP9 were decreased in the T24/B7-H3 shRNA group compared with the control (P<0.05, respectively). Finally, we were able to inhibit tumor development by decreasing B7-H3 expression in vivo. In conclusion, a high expression level of B7-H3 in MIBC tissues is associated with a poor clinicopathological status and poor prognosis, and promotes the development of MIBC in vitro and in vivo. Thus, B7-H3 may be a potential novel biomarker for the poor prognosis of MIBC patients.