论文部分内容阅读
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n χ2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。n 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); n χ2值：9.43、6.81，均n P0.05]。LAG-3阳性表达与肿瘤单发病灶有关[比值比(n OR)＝0.248，95% n CI：0.086～0.716，n P＝0.010]。单因素(n χ2＝4.96, n P＝0.026)和多因素生存分析[风险比(n HR)＝2.239, 95% n CI：1.013～4.592, n 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(n OR: 0.309～3.084，均n P>0.05)，也未发现TIM-3阳性表达与PFS率有关(n χ2＝0.008，n P＝0.929)。n 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 by n χ2 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.n 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); n χ2 values: 9.43, 6.81, both n P0.05). Factors associated with the positive expression of LAG-3 included tumors with a single lesion (odds ratio (n OR)=0.248, 95% n CI: 0.086-0.716, n P=0.010). Log-rank test (n χ2=4.96, n P=0.026) and multivariate Cox regression analysis (hazard ratio (n HR)=2.239, 95% n CI: 1.013-4.592, n 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 (n OR: 0.309-3.084, all n P>0.05) and no association between TIM-3 positive expression and PFS (n χ2=0.008, n P=0.929).n Conclusion:The expressions of LAG-3 and TIM-3 are significantly increased in DTC tissues, and the higher expression of LAG-3 is associated with the worse prognosis, suggesting that LAG-3 may be a potential target for immunotherapy in DTC patients.