Roles of immune inhibitory molecule B7-H4 in cervical cancer.

Recent studies have reported that the immune-regulatory protein B7-H4 is highly expressed in various types of cancer, but little is known concerning its roles in cervical cancer. In the present study, we investigated the expression of B7-H4 in human tissues and serum samples, and explored the effects of B7-H4 on proliferation, apoptosis, migration and invasion of cervical cancer cell lines, including SiHa and HeLa. We found that B7-H4 was mainly located in the cytoplasm of cervical cancer cells as determined by immunofluorescence staining. Serum B7-H4 (sB7-H4) was overexpressed in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer, and the area under the ROC curve (AUC) was 0.955. There was no statistical significance between B7-H4 expression and clinicopathological factors in cervical cancer tissue samples. B7-H4 promoted the proliferation of SiHa and HeLa cells, and protected them from apoptosis, which was related to the upregulation of E7, phosphorylated Rb (pRb), E2F, P16, P21, Bcl-2 and the downregulation of Rb, cleaved PARP and cleaved caspase-3 as determined by western blotting. In addition, B7-H4 increased the ability of cell migration and invasion by targeting angiogenic factors, matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF) as determined by RT-PCR. Our findings revealed that B7-H4 has the potential to be a useful prognostic marker. In addition, B7-H4 plays important roles in proliferation, apoptosis, migration and invasion, indicating that B7-H4 can serve as a new therapeutic target for cervical cancer.