免疫检查点IDO-1、LAG-3、TIM-3与分化型甲状腺癌临床病理特征及预后的相关性  

Correlation of IDO-1, LAG-3 and TIM-3 with clinicopathological features and prognosis of differentiated thyroid cancer

作　　者：陈肖玥 孙健雯 张国强 沈晨天 邱忠领[1] 罗全勇[1] Chen Xiaoyue;Sun Jianwen;Zhang Guoqiang;Shen Chentian;Qiu Zhongling;Luo Quanyong(Department of Nuclear Medicine,Shanghai Sixth People′s Hospital,Shanghai Jiao Tong University,Shanghai 200233,China)

机构地区：[1]上海交通大学附属第六人民医院核医学科,200233

出　　处：《中华核医学与分子影像杂志》2021年第4期196-200,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：上海市重中之重医学影像重点专科(2017ZZ02005);上海市临床重点专科项目(shslczdzk03203)。

摘　　要：目的探究3种免疫检查点吲哚胺2,3-双加氧化酶1(IDO-1)、淋巴细胞活化基因3(LAG-3)、T细胞免疫球蛋白黏蛋白分子3(TIM-3)在分化型甲状腺癌(DTC)中的表达情况以及预后价值。方法回顾性分析2014年5月至2015年11月于上海交通大学附属第六人民医院行手术治疗的119例DTC患者(男33例,女86例,中位年龄42岁)的临床资料。免疫组织化学染色分析IDO-1、LAG-3、TIM-3在甲状腺癌组织和甲状腺正常组织中的表达情况,采用χ^(2)检验分析其阳性表达率的差异。采用logistic回归分析3种免疫检查点与各临床病理因素之间的关系。对患者进行随访,采用Kaplan-Meier法进行单因素生存分析,通过log-rank检验比较组间差异;采用Cox比例风险回归模型进行多因素生存分析。结果119例患者中位随访时间55(2~66)个月,5年无进展生存(PFS)率为76.47%(91/119)。LAG-3、TIM-3在甲状腺癌组织中的阳性表达率分别为21.85%(26/119)和78.15%(93/119),均较甲状腺正常组织更高[7.34%(8/109)和62.39%(68/109);χ^(2)值:9.43、6.81,均P<0.05]。IDO-1在甲状腺癌组织中的阳性表达率为70.59%(84/119),与甲状腺正常组织差异无统计学意义[64.22%(70/109);χ^(2)=1.05,P>0.05]。LAG-3阳性表达与肿瘤单发病灶有关[比值比(OR)=0.248,95%CI:0.086~0.716,P=0.010]。单因素(χ^(2)=4.96,P=0.026)和多因素生存分析[风险比(HR)=2.239,95%CI:1.013~4.592,P=0.046]均提示LAG-3阳性表达是5年PFS率降低的独立危险因素;未发现与TIM-3阳性表达相关的临床病理因素(OR:0.309~3.084,均P>0.05),也未发现TIM-3阳性表达与PFS率有关(χ^(2)=0.008,P=0.929)。结论免疫检查点LAG-3及TIM-3在甲状腺癌组织中表达明显增高,且LAG-3的阳性表达与更差的预后相关,提示LAG-3可能成为DTC免疫治疗的潜在靶点。Objective To explore the expression of indoleamine 2,3-dioxygenase 1(IDO-1),lymphocyte-activation gene 3(LAG-3)and T cell immunoglobulin domain and mucin domain-containing molecule 3(TIM-3)in differentiated thyroid cancer(DTC),and the value of them on prognosis.Methods From May 2014 to November 2015,119 DTC patients(33 males,86 females,media age:42 years)who underwent surgical treatment in Shanghai Sixth People′s Hospital were retrospectively analyzed.The expressions of IDO-1,LAG-3 and TIM-3 in the specimens were analyzed by immunohistochemistry and the expression differences between cancer tissues and normal tissues were analyzed byχ^(2) test.The correlation of IDO-1,LAG-3 and TIM-3 with clinical characteristics were analyzed using logistic regression analysis.The patients were followed up for 5 years,and the relationships of the progression-free survival(PFS)rate with the expressions of the three immune checkpoints were analyzed by Kaplan-Meier method,log-rank test and Cox proportional hazard models.Results The overall 5-year PFS rate for 119 DTC patients(median follow-up time:55(2-66)months)was 76.47%(91/119).The positive expression rates of LAG-3 and TIM-3 in cancer tissues were 21.85%(26/119)and 78.15%(93/119)respectively,which were significantly higher than those in normal thyroid tissues(7.34%(8/109)and 62.39%(68/109);χ^(2) values:9.43,6.81,both P<0.05).While the positive expression rate of IDO-1 was 70.59%(84/119)in cancer tissues,which did not show a significant difference from that in normal thyroid tissues(64.22%(70/109);χ^(2)=1.05,P>0.05).Factors associated with the positive expression of LAG-3 included tumors with a single lesion(odds ratio(OR)=0.248,95%CI:0.086-0.716,P=0.010).Log-rank test(χ^(2)=4.96,P=0.026)and multivariate Cox regression analysis(hazard ratio(HR)=2.239,95%CI:1.013-4.592,P=0.046)suggested that LAG-3 positive expression was an independent risk factor of PFS.The same analysis of TIM-3 found no clinicopathological factors related to TIM-3 positive expression(OR:0.309-3.084,all P

关 键 词：甲状腺肿瘤 吲哚胺-吡咯2 3-双加氧酶 抗原 CD 膜蛋白类 

分 类 号：R736.1[医药卫生—肿瘤]