Roles of B7-H3 in Cervical Cancer and Its Prognostic Value.

B7-H3, which has been reported to be a co-regulatory ligand of the B7 family, can suppress T cell-mediated immunity and has also been reported to be expressed in many malignancies. In this study, we found that B7-H3 was primarily expressed in the cytoplasm of cervical cancer cells and was associated with deep stromal invasion (P=0.0013). The disease-free survival data showed that cervical cancer patients whose tumours were positive for B7-H3 expression had higher mortality rates compared with patients whose tumours lacked B7-H3 expression (P=0.0317), representing an advantage over P16 (P=0.3486). In contrast, the level of serum B7-H3 was low in cases of cervical intraepithelial neoplasia and cervical cancer. The silencing of B7-H3 in the SiHa, CaSki and H8 cell lines inhibited cell proliferation and enhanced apoptosis, while the over-expression of B7-H3 in HeLa cells showed inverse changes. These changes were partially due to the regulation of cell cycle- and apoptosis-related proteins, such as E2F, P21, P16, PARP-1, Caspase-8, Bax, Bcl-2 and Bcl-xl. The results of in vivo experiments revealed that the knockdown of B7-H3 in tumour cells suppressed SiHa cell growth in nude mice. Overall, B7-H3 is involved in the development and progression of cervical intraepithelial neoplasia and cervical cancer through its effects on the cell cycle and apoptosis, which are mediated via the E7/Rb pathway. B7-H3 also has the potential to be a useful prognostic marker for patients with cervical cancer.