Expression of B7-H4 and hepatitis B virus X in hepatitis B virus-related hepatocellular carcinoma

AIM: To investigate the expression and clinical significance of B7-H4 and hepatitis B virus X (HBx) protein in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). METHODS: The expression of B7-H4 in the human HCC cell lines HepG2 and HepG2.2.15 were detected by western blot, flow cytometry, and immunofluorescence. The expression of B7-H4 and HBx in 83 HBV-HCC was detected by immunohistochemistry, and the relationship with clinicopathological features was analyzed. Paraffin sections were generated from 83 HBV-HCC patients (22 females and 61 males) enrolled in this study. The age of these patients ranged from 35 to 77 years, with an average of 52.5 +/- 11.3 years. All experiments were approved by the Ethics Committees of the Second Affiliated Hospital, Zhejiang University School of Medicine. RESULTS: B7-H4 was significantly upregulated in HepG2.2.15 cells compared to HepG2 cells. Specifically, the protein expression of B7-H4 in the lysates of HepG2 cells was more than that in HepG2.2.15 cells. In addition, HBx was expressed only in HepG2.2.15 cells. Similar data were obtained by flow cytometry. The positive rates of B7-H4 and HBx in the tissues of 83 HBV-HCC patients were 68.67% (57/83) and 59.04% (49/83), respectively. The expression of HBx was correlated with tumor node metastases (TNM) stage, and the expression of B7-H4 was positively correlated with HBx (r(s) = 0.388; P < 0.01). The expression level of B7-H4 in HBx-positive HBV-HCC tissues was substantially higher than that in HBx-negative HBV-HCC tissues. The expression level of B7H4 was negatively related to tumor TNM stage. CONCLUSION: Higher expression of HBx and B7-H4 was correlated with tumor progression of HBV-HCC, suggesting that B7-H4 may be involved in facilitating HBV-related hepatocarcinogenesis.