Objective: To analyze the potential clinical relevance of inhibitory immune checkpoint genes, including PD1, PD-L1, CTLA4, LAG3 and TIM3 in esophageal squamous cell carcinoma (ESCC). Methods: Expression were extracted from mRNA microarray data from 119 paired ESCC and adjacent normal tissues, which were collected from National Cancer Center/Chinese Academy of Medical Sciences between December 2005 and December 2007.Differential expression analyses and survival analyses were then performed to identify potential clinical relevance using R software. Results: Expression of PD-L1, CTLA4, LAG3 and TIM3 were significantly upregulated in ESCC tissues compared with adjacent normal tissues (P<0.05). CTLA4 was significantly correlated with tumor location and age (P<0.05). PD1 and LAG3 were significantly associated with overall survival and were favorable prognostic factors in ESCC. Conclusions: Inhibitory immune checkpoint genes are commonly overexpressed in ESCC and are significantly associated with patients overall survival.These results provide important references in the application of immune checkpoints therapy in ESCC.
目的： 分析抑制性免疫检查点基因细胞程序性死亡受体1(PD1)，细胞程序性死亡配体1(PD－L1)，人细胞毒性T淋巴细胞相关抗原4(CTLA4)，淋巴细胞激活基因3蛋白(LAG3)，T细胞免疫球蛋白黏蛋白3(TIM3)与食管鳞癌的临床相关性。 方法： 119例配对食管鳞癌组织和癌旁正常组织样本来自于2005年12月至2007年12月在国家癌症中心中国医学科学院肿瘤医院接受手术治疗的食管鳞癌患者，从其mRNA芯片数据中提取免疫检查点基因的表达水平，通过R语言程序进行差异表达、临床相关和生存分析。 结果： PD－L1、CTLA4、LAG3和TIM3在食管鳞癌组织中的表达显著高于癌旁正常组织中的表达(均P<0.05)。CTLA4与肿瘤位置和年龄有显著相关性(P<0.05)。PD1和LAG3与总体生存显著相关(P<0.05)，高表达的PD1和LAG3提示好的预后，该结果在TCGA数据库的头颈鳞癌中得到验证。 结论： 抑制性免疫检查点基因在食管鳞癌中普遍显著高表达，并且与食管鳞癌患者总体生存显著相关，为免疫检查点阻滞疗法在食管鳞癌中的应用提供了重要参考。.
Keywords: Esophageal neoplasms; Genes, suppressor; Prognosis.