共刺激分子B7-H4在胃癌组织中表达及其与预后的关系

Expression of costimulatory molecule B7-H4 in the gastric carcinoma tissues and its correlation with prognosis

目的探讨共刺激分子B7-H4在胃癌组织中的表达与预后的关系。方法应用免疫组织化学染色，检测156例胃癌患者手术标本中B7-H4的表达；应用生物技术，体外诱导自体细胞因子激活的杀伤细胞（CIK）进行免疫治疗胃癌。结果B7-H4在胃癌组织中阳性表达率为44．9％；单因素分析显示，B7-H4的表达与性别、年龄、组织学类型、病理分级、肿瘤大小等均无明显相关；但浸润深度和淋巴结转移与B7-H4阳性表达显著关联，侵入肌层组的B7-H4阳性率高于未侵入组（49．1％比16．7％），差异有统计学意义（X^2=8．467，P=0．01），淋巴结转移组B7-H4阳性率高于未转移组（X^2=17．339，P〈0．01）。与B7-H4高表达组比较，B7-H4低表达组胃癌患者中位生存时间显著延长13个月，差异有统计学意义（，=12．38，P〈0．01）。多因素COX模型分析显示，与B7-H4低表达组比较，B7-H4高表达组胃癌患者的死亡风险明显增加（RR=1．85，95％CI=1．15～2．96）；CIK治疗组与化疗组比较，CIK治疗组胃癌患者的死亡风险明显降低（RR=0．53，95％CI=0．33—0．85）。结论B7．H4的高表达与胃癌患者的生存时间成负相关，证实了B7-H4为一负性调节分子，可作为判断胃癌生存期的指标；CIK细胞治疗可以显著延长胃癌患者的生存期。

Objective To-study the expression of costimulatory molecules B7-H4 in the gastric carcinoma tissues and its correlation with prognosis. Methods B7-H4 expression in the surgical specimens of gastric cancer tissues was detected by using immunohistochemistry in 156 patients who had obtained either autologous cytokine-induced killer （CIK） cell biotherapy or chemotherapy. Results Positive expression rate of B7-H4 in gastric carcinoma tissues was 44.9%. Single-factor analysis demonstrated that there was no correlation between the BT-H4 expression and sex, age, histological type, pathological grade or tumor size. However, there was a statistically significant correlation between the B7-H4 positive expression and the invasion depth and lymph node metastasis. The positive expression rate of B7-H4 was obviously higher in the invasive group than in the non-invasive group （49.1% vs 16.7% ,X^2 = 8. 467 ,P 〈 0.01 ）. And the positive expression rate of B7-H4 was higher in the lymph node metastasis group than in the nonmetastasis group （X^2 = 17. 339 ,P 〈0.01 ）. The median survival time of gastric cancer patients with B7-H4 low expression was 13 months longer than in those with high expression （X^2=12.38 ,P 〈0.01 ）. Multi-factor COX model analysis demonstrated that the B7-H4 expression may be considered as the prediction of survival time in the gastric cancer patients （RR = 1.85,95% CI = 1. 15-2.96）. Moreover, the risk of death in gastric cancer patients was significantly lower in the CIK treatment group than in the chemotherapy group （ RR = 0.53,95 % CI = 0.33-0.85 ）. Conclusion There was a negative correlation between the high expression of BT-H4 and the survival time of gastric cancer patients ,which may suggest that BT-H4 is one of negative regulatory molecules and may be considered as a predictive index of gastric cancer patients. CIK cells treatment can significantly prolong the survival time.