胆囊腺癌演变过程中B7-H3蛋白和CD3^+、CD8^+T细胞表达及预后分析

Expression and prognosis of B7-H3 protein and CD3^+,CD8^+T cells during the progression of gallbladder adenocarcinoma

目的探讨B7-H3蛋白在胆囊腺癌演变过程中不同阶段的表达和胆囊腺癌微环境中浸润CD3^+和CD8^+T细胞的表达及与预后的关系。方法采用免疫组织化学法检测B7-H3蛋白在癌旁正常组织、胆囊息肉、胆囊腺瘤、高级别上皮内瘤变和胆囊腺癌组织中的表达和胆囊腺癌间质中浸润CD3^+、CD8^+T细胞的表达,并分析其与胆囊腺癌临床病理特征及预后的关系。结果B7-H3蛋白在癌旁正常组织、胆囊息肉、胆囊腺瘤、高级别上皮内瘤变和胆囊腺癌组织中的阳性表达率分别为0、30.0%、32.5%、48.0%、69.0%。CD3^+和CD8^+T细胞在胆囊腺癌中的阳性表达率分别为81.0%和62.1%,在癌旁正常组织中无表达。B7-H3蛋白表达与胆囊腺癌的分化程度、TNM分期、、是否伴胆囊结石、肿瘤直径和淋巴结转移有关(P<0.05),而与年龄和性别无关(P>0.05)。Pearson相关性分析显示,胆囊腺癌中B7-H3与CD3^+T细胞的表达呈正相关(r=0.455,P=0.025)。B7-H3蛋白高表达和低表达组的中位生存期(OS)分别为15个月和23个月,差异有统计学意义(P=0.037)。CD3^+T细胞高表达和低表达组的中位OS分别为27个月和17个月,差异有统计学意义(P=0.035)。CD8^+T细胞高表达和低表达组的中位OS分别为15个月和13个月,差异无统计学意义(P>0.05)。结论B7-H3蛋白和CD3^+T细胞可能在胆囊腺癌的演变过程中发挥重要的作用,并与预后密切相关。

Objective To investigate the expression of B7-H3 protein in different stages of gallbladder adenocarcinoma and the infiltration of CD3^+and CD8^+T cells in the microenvironment of gallbladder adenocarcinoma.Methods Immunohistochemistry was used to detect the expression of B7-H3 protein in paracancerous normal tissue,gallbladder polyps,gallbladder adenomas,high-grade intraepithelial neoplasia and gallbladder adenocarcinom tissues,and the expression of infiltrating CD3^+and CD8^+T cells in gallbladder adenocarcinoma.Then the relationship between their expression and clinicopathological characteristics,prognosis of gallbladder adenocarcinoma was analyzed.Results The expression rate of B7-H3 protein was 0,30.0%,32.5%,48.0%,69.0%in normal tissues adjacent to cancer,gallbladder polyps,gallbladder adenoma,high-grade intraepithelial neoplasia and gallbladder adenocarcinoma tissue.The positive expression rates of CD3^+and CD8^+T cells in gallbladder adenocarcinoma were 81.0%and 62.1%,respectively,and there was no expression in normal tissues adjacent to cancer.The expression of B7-H3 protein was significantly correlated with pathological grade,TNM stage,whether or with gallstones,tumor diameter and lymph node metastasis of gallbladder adenocarcinoma(P<0.05),but not related to age and gender(P>0.05).The expression of B7-H3 and CD3^+T cells were positively correlated in gallbladder adenocarcinoma(r=0.455,P=0.025).The median overall survival(OS)of B7-H3 protein high expression group and low expression group was 15 months and 23 months respectively,and the difference was statistically significant(P=0.037).The median OS of CD3^+T cell high expression group and low expression group was 27 months and 17 months respectively,and the difference was statistically significant(P=0.035).The median OS of CD8^+T cell high expression group and low expression group was 15 months and 13 months respectively,and the difference was not statistically significant(P>0.05).Conclusion B7-H3 protein and CD3^+T lymphocytes may play an important role in the evolution of gallbladder adenocarcinoma and are closely related to the prognosis.