Aberrant expression of B7-H4 may contribute to the development of hepatocellular carcinoma

In order to determine the effect of B7-H4 on the development of human hepatocellular carcinoma (HCC), the expression levels of B7-H4 were evaluated using reverse transcription-polymerase chain reaction and flow cytometry in HL-7702 and Huh7 cells. B7-H4 protein expression levels were analyzed using western blotting and immunohistochemistry in HCC tissues collected from patients and from a mouse tumor model. Soluble B7-H4 (sB7-H4), interferon-γ (IFN-γ), and interleukin-4 (IL-4) in blood serum were assessed using ELISA in patients with HCC and mice injected with tumor cells. B7-H4 was expressed in HCC cell lines, mouse tumor tissues and HCC patient tissues. However, B7-H4 was not detected in HL-7702 cells or normal human liver tissues. The expression level of B7-H4 was positively correlated with tumor-node-metastasis (TNM) stage, lymph node metastasis, and differentiation degree in patients with HCC. sB7-H4 levels in blood serum samples collected from patients with HCC and tumorigenic mice were higher compared with healthy controls. Expression levels of IFN-γ were reduced, and IL-4 levels were increased in blood serum samples of patients with HCC and tumorigenic mice compared with healthy controls. sB7-H4 expression levels were negatively correlated with IFN-γ levels, and with the ratio of IFN-γ to IL-4. Additionally, sB7-H4 was positively correlated with IL-4 levels in mouse tumor tissues, serum samples obtained from tumorigenic mice and human HCC patients. Notably, the levels of sB7-H4 and IL-4 were positively correlated and IFN-γ was negatively correlated with the TNM stage of patients with HCC. In addition, sB7-H4 and IL-4 expression levels increased and levels of IFN-γ and the ratio of IFN-γ/IL-4 decreased as a function of time post tumor implantation in the mouse model. The present study determined that aberrant expression of B7-H4 contributed to HCC development. B7-H4 may be a potential target for therapy and diagnosis of HCC.