TAP-1、TAP-2及HLA-I在鼻咽癌中的表达及临床意义  

Expressions of TAP-1 and TAP-2 and human leukocyte antigenⅠin nasopharyngeal carcinoma and clinical significance

作　　者：任艳鑫[1] 李晓江[1] 张丽娟[2] 杨洁[1] 孙瑞梅[1] 张世文[1] 张吉[1] 

机构地区：[1]昆明医科大学第三附属医院头颈肿瘤研究中心,云南昆明650118 [2]昆明医科大学第三附属医院病理科,云南昆明650118

出　　处：《西安交通大学学报（医学版）》2014年第4期527-532,546,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81260312);云南省卫生科技内设研究机构项目资助(No.2011 WS0068);云南省社会发展科技计划(应用基础研究重点项目)(No.2009CC026)~~

摘　　要：目的探讨鼻咽癌组织中MHC-I类分子抗原加工提呈"操纵子"(即TAP-1、TAP-2及HLA-I)表达的变化及其与临床因素的关系。方法免疫组织化学法(IHC)检测鼻咽癌石蜡切片中TAP-1、TAP-2及HLA-I的表达,采用流式细胞仪(FCM)检测鼻咽癌患者及对照组外周血中CD4+T、CD8+T细胞比例,应用酶联免疫吸附法(ELISA)检测空腹外周静脉血IL-10含量,并对以上结果进行统计分析。结果 TAP-1、TAP-2及HLA-I在鼻咽癌组织中表达分别为43.1%、46.55%、50%,均低于鼻咽正常组织中的表达90%、95%、95%(P<0.05);鼻咽癌组CD4+T细胞比例明显低于对照组[(33.41±10.04)%vs.(40.15±3.56)%](P<0.05),CD8+T细胞比例与对照组比较差异无统计学意义[(25.32±8.29)%vs.(22.89±2.24)%,P>0.05],鼻咽癌IL-10表达明显高于对照组[(13.12±1.23)ng/mL vs.(3.69±1.03)ng/mL,P<0.05];TAP-1、TAP-2及HLA-I表达与年龄、性别无相关性(P>0.05),与TNM分期、有无淋巴结转移及有无远处转移密切相关(P<0.05);CD8+T细胞比例与TAP-1、TAP-2及HLA-I表达成正比,IL-10表达与TAP-1、TAP-2及HLA-I表达成反比,而CD4+T细胞比例与TAP-1、TAP-2及HLA-I表达无明显相关性;Kaplan-Meier分析提示,临床分期、有无淋巴结转移、有无远处器官转移、病理分型、TAP-1表达、TAP-2表达、HLA-I表达与鼻咽癌患者预后相关,差异具有统计学意义(P<0.05);Logistic回归模型分析显示,有无远处器官转移及HLA-I表达为鼻咽癌患者独立预后因素(P=0.043,P=0.045)。结论鼻咽癌中TAP-1、TAP-2及HLA-I低表达,且与患者免疫功能低下相关;远处器官转移及HLA-I低表达预示鼻咽癌患者预后不良。Objective To determine the expression of MHC-Ⅰ antigen processing ＂the operons＂,namely,transporter associated with antigen processing 1 （TAP-1）,transporter associated with antigen processing 2 （TAP-2）,and human leukocyte antigen Ⅰ （HLA-Ⅰ） in nasopharyngeal carcinoma （NPC） and explore the relationship between their expressions and the clinical factors.Methods We analyzed the expressions of TAP-1,TAP-2 and HLA-Ⅰ by immunohistochemistry; the percentage of CD4＋T cells and CD8＋T cells in peripheral blood （PB） of NPC patients or normal subjects by flow cytometry; and the content of IL-10 in PB by enzyme linked immunosorbent assay.Results The expressions of TAP-1,TAP-2 and HLA-Ⅰ in NPC were 43.1％,46.55％ and 50％,which were significantly lower than those in control group,respectively （P＜0.05）.The percentage of CD4＋T cells in NPC group was obviously lower than that in control group [（33.41±10.04）％ vs.（40.15±3.56）％]（P＜0.05） while CD8＋T cells increased slightly without significant differences compared with that in control group [（25.32 ±8.29）％ vs.（22.89±2.24）％] （P＞0.05）.IL-10 expression was obviously higher in NPC than in control group [（13.12 ± 1.23） ng/mL vs.（3.69 ± 1.03） ng/mL] （P＜0.05）.TAP-1,TAP-2 and HLA-Ⅰ expressions had no correlation with age or gender （P＞0.05）,but were closely associated with TNM phase,lymph gland metastasis or not and distance metastasis or not （P＜0.05）.CD8＋T cells percentage was positively correlated with TAP-1,TAP-2 and HLA-Ⅰ expressions.IL-10 expression had a negative correlation with TAP-1,TAP-2 and HLA-Ⅰ expressions.CD8＋T cells percentage had no correlation with TAP-1,TAP-2 and HLA-Ⅰ expressions.Clinical phase,lymph gland metastasis or not,distant organ metastasis or not,pathological type,TAP-1 expression,TAP-2 expression and HLA-Ⅰ expression were prognostic factors by Kaplan-Meier analysis （P＜ 0.05）.Multivariate survival analysis showed that distant met

关 键 词：鼻咽癌 抗原处理相关转运体蛋白-1 抗原处理相关转运体蛋白-2 人类白细胞抗原-I 转移 

分 类 号：R739.63[医药卫生—肿瘤]