Abstract: OBJECTIVE: To investigate the costimulatory molecule B7 homolog 4 (B7-H4) expression during progression of esophageal precancerous lesions in mice and to evaluate its clinical significance in esophageal squamous cell carcinoma formation. METHODS: 133 C57BL/6 mice were assigned to the control group (n=42) or 4NQO model group (n=91). 50 μg/mL 4-Nitroquinoline -1-oxide (4NQO) in drinking water was fed to the 4NQO model mice for 15 weeks. Hematoxylin eosin (HE) staining was used to evaluate changes in pathological stages of esophageal tissues. B7-H4 protein expression in esophageal tissues was detected by immunohistochemical staining and Western blot. B7-H4 protein expression in serum was detected by Western blot. RESULTS: From 16th to 28th week,esophageal showed visible pathological changes,such as incrassation,pimplings and lumps. Furthermore,HE staining showed that there was a significant and positive correlation between the esophageal pathological grade and the induction time of carcinogenesis,(r=0.55,P < 0.01). Additionally,B7-H4 protein expression in esophageal tissue was positively correlated with the pathological grade of precancerous lesions(r=0.57,P < 0.01). At 26 th and 28 th week, B7-H4 protein expression increased significantly compared with the control group(P < 0.05 or P < 0.01). Moreover, B7-H4 protein concentration in sera of mice of high grade intraepithelial neoplasia increased significantly compared with the normal mice,P < 0.05. CONCLUSION: B7-H4 expression in esophageal and sera increased gradually during the progression of esophageal precancerous lesions. Therefore,B7-H4 may be involved in the formation of esophageal precancerous conditions.

Key words: 4NQO, costimulatory molecule, B7-H4, esophageal precancerous condition