协同刺激分子B7-H4在食管癌前病变组织中的表达及临床意义

目的：研究协同刺激分子B7同系物4（B7-H4）在人食管癌前病变组织中的表达变化，探讨其在食管鳞状细胞癌形成中的临床意义。方法：收集内镜切除的食管组织标本58例，其中正常组织16例，低级别上皮内瘤变（LGIN）23例，高级别上皮内瘤变（HGIN）19例。通过苏木素-伊红（HE）染色评价食管组织病理变化。分别采用实时荧光定量PCR（qPCR）检测B7-H4 mRNA在食管组织的表达；免疫组织化学和Western blot检测B7-H4蛋白在食管病变组织中的表达；酶联免疫吸附法（ELISA）检测食管组织细胞因子IL-6、IL-10和IFN-γ的表达，并分析各细胞因子与B7-H4蛋白表达的相关性。结果：免疫组化和HE染色结果提示，B7-H4表达与食管组织病理分级呈显著正相关（P < 0.01）。qPCR结果提示，与正常食管组织相比，食管癌前病变组织B7-H4 mRNA表达无显著改变（P > 0.05）。而Western blot实验结果显示，与正常食管组织相比，食管癌前病变组织B7-H4蛋白表达显著升高（P < 0.05）。Westernblot和ELISA实验结果显示B7-H4表达与IL-6表达呈正相关（P < 0.01）。结论：随着食管癌前病变病理分级的提高，B7-H4蛋白的表达逐渐上调，B7-H4可能与IL-6相互作用促进了食管鳞状细胞癌的发生发展。

Clinical significance in expression of costimulatory molecule B7-H4 in precancerous esophageal tissues

OBJECTIVE:To study expression of a costimulatory molecule, B7 homologue 4 (B7-H4), in precancerous lesions of human esophageal carcinoma and to understand its clinical significance in the formation of esophageal squamous cell carcinoma. METHODS:58 esophageal tissue specimens of endoscopic resection were collected. There were 16 cases of normal tissues,23 cases of low-grade intraepithelial neoplasia (LGIN) and 19 cases of high-grade intraepithelial neoplasia (HGIN). Hematoxylin eosin staining (HE) was used to evaluate their pathological changes. Expression of B7-H4 mRNA in esophageal tissues was detected by real-time fluorogenic quantitative-PCR (qPCR). Immunohistochemistry and Immunoblotting (Western blot) methods were used to detect B7-H4 protein expression in esophageal tissues. Expressions of IL-6, IL-10 and IFN-γ in esophagi were detected by Enzyme-linked Immunosorbent assay (ELISA). Additionally,correlations between expression of these cytokines and B7-H4 protein were analyzed. RESULTS:Immunohistochemistry and HE results indicate that B7-H4 protein expression was positively correlated with esophageal pathological grade (P < 0.01). Moreover,the qPCR results show that there was no significant difference in expression of B7-H4 mRNA between precancerous tissues and normal esophageal tissues (P > 0.05). Western blot data indicate that B7-H4 protein expression was increased significantly in precancerous esophagi compared with that of normal esophagi (P < 0.05). Furthermore,results of Western blot and ELISA tests show that B7-H4 expression was positively correlated with IL-6 concentration (P < 0.01). CONCLUSION:B7-H4 protein expression was gradually upregulated with the increase of precancerous grade of esophagi. B7-H4 may promote esophageal squamous cell carcinoma formation by interacting with IL-6.