癌胚抗原相关细胞黏附分子1在胶质瘤中的表达及其临床意义  

Clinical significance of expression of circulating and tumor-infiltrating carcinoembryonic antigen-related cell adhesion molecule 1 in patients with glioma

作　　者：刘晓东[1] 李晋虎 陈春美[2] 范益民[1] 王宏勤 郑安潮[1] 陈毅[1] 韩杰 Liu Xiaodong;Li Jinhu;Chen Chunmei;Fan Yimin;Wang Hongqin;Zheng Anchao;Chen Yi;Han Jie(Department of Neurosurgery,the First Affiliated Hospital,Shanxi Medical University,Taiyuan 030001,China;Department of Neurosurgery,Union Medical College Hospital,Fujian Medical University,Fuzhou 350001,China)

机构地区：[1]山西医科大学第一医院神经外科,大原030001 [2]福建医科大学附属协和医院神经外科,福州350001

出　　处：《中华实验外科杂志》2020年第3期544-547,共4页Chinese Journal of Experimental Surgery

基　　金：山西省应用基础研究计划面上青年基金项目(201901D211478);山西医科大学第一医院院博士基金(YB161714)。

摘　　要：目的观察脑胶质瘤患者肿瘤浸润及静脉血T淋巴细胞中癌胚抗原相关细胞黏附分子1(CEACAM1)的表水平,并对CEACAM1和脑胶质瘤患者的临床病理因素进行相关分析。方法收集2013年5月至2018年2月山西医科大学第一医院神经外科手术切除的病理资料齐全的新鲜胶质瘤组织92例,获取肿瘤浸润T淋巴细胞(TIL组)及同一患者静脉血单核细胞(PBMC组),收集健康志愿者PBMCs 35例及颅脑损伤切除脑组织15例(对照组)。提纯获取肿瘤浸润T淋巴细胞(TILs)及获取相同患者静脉血单核细胞(PBMCs),健康对照组收集健康志愿者的PBMCs 35例及重型颅脑损伤手术切除脑组织15例。通过流式细胞术检测T淋巴细胞表面CEACAM1的表达水平,通过免疫组织化学检测CEACAM1在脑组织和胶质瘤组织中的表达,分析CEACAM1与人脑胶质瘤病理分级、卡氏评分(KPS评分)、γ-干扰素(IFN-γ)等多种临床病理因素之间以及CEACAM1在胶质瘤和T淋巴细胞表达之间的相关性。组间比较及相关分析分别采用Student’s t检验及Spearman’s秩相关检验。结果胶质瘤患者PBMCs中CEACAM1阳性细胞表达率和平均荧光强度均增加,TILs中表达进一步增加[阳性表达率为CD4:TIL(6.01±0.21)%、G-PBMC(3.04±0.15)%、C-PBMC(0.95±0.10)%,t=11.380、8.190;CD8:(5.52±0.19)%、(3.54±0.15)%、(0.97±0.88)%,t=8.130、10.140;P<0.05;平均荧光强度为CD4:TIL 7.34±0.29、G-PBMC 4.22±0.22、C-PBMC 2.06±0.17,t=8.610、5.860;CD8:6.04±0.26、3.50±0.18、1.46±0.13,t=8.140、6.820,P<0.05];CEACAM1在高级别胶质瘤患者PBMCs中CD4+和CD8+T细胞的表达升高[CD4:Ⅰ~Ⅱ级(2.05±0.16)%;Ⅲ~Ⅳ级(3.47±0.18)%,t=4.960,P<0.05;CD8:Ⅰ~Ⅱ级(2.34±0.20)%;Ⅲ~Ⅳ级(4.12±0.16)%,t=6.670,P<0.05],且在TILs中表达进一步升高[CD4:Ⅰ~Ⅱ级:(3.87±0.33)%;Ⅲ~Ⅳ级(6.37±0.22)%,t=6.470,P<0.05;CD8:Ⅰ~Ⅱ级(4.45±0.27)%、Ⅲ~Ⅳ级(6.24±0.20)%,t=5.140,P<0.05];胶质瘤患者TILs和PBMCs中CD4+T细胞上的CEACAM1的表达同患者KObjective To observe the levels of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)in tumor invasion of glioma patients and venous blood T lymphocytes,and to evaluate the correlation between the levels of CEACAM1 and clinicopathological features of glioma patients.Methods Ninety-two cases of fresh glioma tissues with complete pathological data collected from Department of Neurosurgery of the First Hospital of Shanxi Medical University were obtained,and tumor-infiltratinglymphocytes(TILs)were obtained,and peripheral blood mononuclear cells(PBMCs)from the same patients.PBMCs from healthy control group(35 cases of from healthy volunteers)and severe brain injury after surgical resection group(15 cases)were also obtained.The expression level of CEACAM1 on the surface of T lymphocytes was detected by flow cytometry,and the expression level of CEACAM1 in brain tissue and glioma tissue was detected by immunohistochemistry.The correlation between CEACAM1 and KPS score,interferon-γ(IFN-γ)and other clinicopathological factors,and correlation between CEACAM1 expression in glioma and T lymphocytes were analyzed.Results Compared with the healthy control group,the positive expression rate of CEACAM1+CD4+T and CEACAM1+CD8+T in PBMCs of glioma patients and mean fluorescence intensity increased,and the expression in TILs of glioma patients increased further[positive expression rate:CD4+T cells:TIL(6.01±0.21)%;G-PBMC(3.04±0.15)%;C-PBMC(0.95±0.10)%,t=11.380,8.190;CD8+T cells:TIL:(5.52±0.19)%;G-PBMC:(3.54±0.15)%;C-PBMC:(0.97±0.88)%;t=8.130,10.140,P<0.05;average fluorescence intensity:CD4+T cells:TIL:7.34±0.29;G-PBMC:4.22±0.22;C-PBMC:2.06±0.17,t=8.610,5.860;CD8+T cells:TIL:6.04±0.26;G-PBMC:3.50±0.18;C-PBMC:1.46±0.13;t=8.140,6.820,P<0.05];the expression of CEACAM1 on CD4+and CD8+T cells in PBMCs of high-grade was increased[CD4+T cells:gradeⅠ-Ⅱ:(2.05±0.16)%;gradeⅢ-Ⅳ:(3.47±0.18)%;t=4.960,P<0.05;CD8+T cells:gradeⅠ-Ⅱ,(2.34±0.20)%;gradeⅢ-Ⅳ:(4.12±0.16)%;t=6.670,P<0.05],and further increased

关 键 词：胶质瘤 免疫检查点分子 癌胚抗原相关细胞黏附分子1 免疫治疗 

分 类 号：R739.4[医药卫生—肿瘤]