CD94和NKG2A在胃癌中的表达与临床特征相关性研究  

Correlation study of CD94 and NKG2A expression and clinical features in gastric cancer

作　　者：刘晨 范佩文 冯亚宁 王海江[1] 王若峥[1,2,3,4] LIU Chen;FAN Peiwen;FENG Yaning;WANG Haijiang+;WANG Ruozheng(Xinjiang Key Laboratory of Oncology,the Third Affiliated Teaching Hospital of Xinjiang Medical University;Key Laboratory of Cancer Immunotherapy and Radiotherapy,Chinese Academy of Medical Sciences;Clinical Key Specialty of Radiotherapy,Health and Welfare Commission;Xinjiang Clinical Research and Cultivation Center for Cancer Radiotherapy,Urumqi 830011,China)

机构地区：[1]新疆医科大学第三临床医学院新疆肿瘤学重点实验室 [2]中国医学科学院肿瘤免疫与放疗研究重点实验室 [3]新疆放射治疗临床重点专科 [4]新疆肿瘤放射治疗临床研究培育中心,乌鲁木齐830011

出　　处：《新疆医科大学学报》2024年第12期1563-1571,共9页Journal of Xinjiang Medical University

基　　金：上海合作组织科技伙伴计划及国际科技合作计划项目(2020E1056)。

摘　　要：目的探讨胃癌患者癌组织、癌旁组织和外周血中CD4^(+)T、CD8^(+)T细胞上CD94和NKG2A表达差异及其与临床特征的相关性。方法收集2022年1月-2023年12月新疆医科大学第三临床医学院附属肿瘤医院,初治且可行手术的胃癌患者,最终入组43例癌组织、37例癌旁组织以及14例患者治疗前的外周血;通过流式细胞术检测外周血单个核细胞、癌组织肿瘤浸润淋巴细胞及癌旁组织中CD4^(+)T、CD8^(+)T细胞上CD94、NKG2A的表达,分析对比其表达以及与胃癌临床特征的相关性。结果(1)CD94^(+)CD8^(+)T细胞群在癌组织中的表达高于外周血和癌旁组织(P均<0.05),NKG2A^(+)CD4^(+)T细胞群在癌组织中的表达高于癌旁组织,NKG2A^(+)CD8^(+)T、CD94^(+)NKG2A^(+)CD8^(+)T细胞群在癌组织中的表达高于外周血(P均<0.001)。(2)在癌组织CD8^(+)T细胞群中,NKG2A^(+)亚群PD-1、CD103、Tim3的表达高于NKG2A+-亚群(P<0.001)。(3)癌组织和外周血中CD94^(+)NKG2A^(+)CD8^(+)T细胞群的高表达与患者p53(+)状态显著相关(P<0.05)。(4)使用Kaplan-Meier plotter分析显示,CD94、NKG2A和HLA-E的高表达提示GC患者OS和FP明显延长(P<0.05)。结论在胃癌组织中,CD94和NKG2A高度表达;NKG2A具有组织驻留记忆性T细胞的特点;CD94^(+)NKG2A^(+)与p53表达存在相关性。CD94、NKG2A可能是对胃癌发生发展,疗效有预测作用的T细胞生物标志物及有效的T细胞免疫治疗标靶。ObjectiveTo investigate the expression differences of CD94 and NKG2A on CD4^(+)T and CD8^(+)T cells in cancer tissues,adjacent tissues and peripheral blood of the patients with cancer and its correlation with clinical characteristics.MethodsFrom January 2022 to December 2023,newly treated and operable gastric cancer patients were collected in the hospital.Finally,43 cases of cancer tissues,37 cases of adjacent tissues and 14 cases of peripheral blood before the treatment were enrolled.The expression of CD94 and NKG2A on CD4^(+)T and CD8^(+)T cells in peripheral blood mononuclear cells,tumor infiltrating lymphocytes in cancer tissues and adjacent tissues was detected by flow cytometry.The correlation between the expression and the clinical characteristics of gastric cancer was analyzed and compared.Results(1)The expression of CD94^(+)CD8^(+)T cells in cancer tissues was higher than that in peripheral blood and para-cancer tissues(both P<0.05),the expression of NKG2A^(+)CD4^(+)T cell group in cancer tissue was higher than that in para-cancer tissue.The expressions of NKG2A^(+)CD8^(+)T and CD94^(+)NKG2A^(+)CD8^(+)T cells in cancer tissues were higher than those in peripheral blood(both P<0.001).(2)The expression of PD-1,CD103 and Tim3 in NKG2A^(+)subgroup was higher than that in NKG2A+-subgroup in CD8^(+)T cells of cancer tissues of the patients(P<0.001).(3)The high expression of CD94^(+)NKG2A^(+)CD8^(+)T cells in cancer tissues and peripheral blood were significantly correlated with the status of p53(+)(P<0.05).(4)Kaplan-Meier plotter analysis showed that the high expression of CD94,NKG2A and HLA-E suggested that the OS and FP of GC patients were significantly prolonged(P<0.05).ConclusionCD94 and NKG2A are prominently expressed in gastric cancer.NKG2A has the characteristic of tissue-resident memory T cells.CD94^(+)NKG2A^(+)is correlated with p53 expression.CD94 and NKG2A may be predictive biomarkers and effective target for T cell immunotherapy in the development and progression of gastric cancer.

关 键 词：胃癌 CD8^(+)T细胞 CD94 NKG2A 临床特征 预后 

分 类 号：R735.2[医药卫生—肿瘤]