胃窦癌组织中LAG-3 FGL1 MHC-Ⅱ的表达与预后的关系

Relationship of LAG-3, FGL1, and MHC-Ⅱ expression with prognosis in gastric antralcancer

目的:探索新型免疫检查点淋巴细胞激活基因3(lymphocyte-activation gene 3,LAG-3)、纤维蛋白原样蛋白1(fibrinogenlike protein 1,FGL1)、主要组织相容性复合体Ⅱ类分子(major histocompatibility complex classⅡ,MHC-Ⅱ)在胃窦癌(gastric antral cancer,GAC)中的表达情况与预后的相关性。方法:收集2012年1月至2014年12月于天津医科大学肿瘤医院诊断为GAC的67例患者病理标本,分别进行石蜡切片制作,采用免疫组织化学法检测LAG-3、FGL1、MHC-Ⅱ三个指标的表达情况,并用统计学方法分析组间差异。采用Kaplan-Meier法评估LAG-3、FGL1、MHC-Ⅱ的表达水平与GAC患者预后之间的关系并绘制生存曲线。结果:GAC患者中,肿瘤大小<4 cm的患者和无淋巴结转移的患者LAG-3免疫细胞阳性率更高(P<0.05);女性患者MHC-Ⅱ免疫细胞阳性率更高(P<0.05)。免疫细胞中LAG-3、MHC-Ⅱ高表达的患者总生存期(overall survival,OS)较好(P<0.05);肿瘤细胞中MHC-Ⅱ高表达的患者OS、无病生存期(disease-free survival,DFS)较差(P<0.05);而FGL1在免疫细胞和肿瘤细胞中的表达与OS、DFS无显著相关性(P>0.05)。结论:GAC患者LAG-3、MHC-Ⅱ在不同区域的表达量存在差异,GAC患者LAG-3及其配体在免疫细胞的表达对预后产生积极影响,提示免疫细胞中LAG-3/MHC-Ⅱ可以作为GAC患者预后标志物,为临床个体化免疫治疗提供新的依据。

Objective:To investigate the expression of the immune checkpoint lymphocyte-activation gene 3(LAG-3),fibrinogen-like protein 1(FGL1),and major histocompatibility complex class II(MHC-II)in gastric antral cancer(GAC)and determine their correlation with disease prognosis.Methods:The expression of LAG-3,FGL1,and MHC-II was analyzed in 67 patients with GAC admitted to Tianjin Medical University Cancer Institute&Hospital from January 2012 to December 2014 using immunohistochemistry.Variations between the groups were analyzed using statistical methods.The Kaplan-Meier method was used to evaluate the relationship between the LAG-3,FGL1,and MHC-II expression levels and the prognosis of patients with GAC.Results:LAG-3 expression level in immune cells was higher in patients with GAC presenting with a tumor size of<4 cm and in those without lymph node metastasis(P<0.05).Further,MHC-II expression level in immune cells was higher in female than in male patients(P<0.05).Patients with high LAG-3 and MHC-II expression levels in immune cells had better overall survival(OS,P<0.05);whereas,patients with high MHC-II expression levels in tumor cells had worse OS and disease-free survival(DFS,P<0.05).However,FGL1 expression in immune cells and tumor cells was not significantly correlated with OS and DFS(P>0.05).Conclusions:The LAG-3 and MHC-II expression levels in various regions of patients with GAC differ,and the expression of LAG-3 and its ligands in the immune cells of patients have a positive impact on prognosis.This suggests that LAG-3 and MHC-II in immune cells can be used as prognostic markers of GAC,providing a novel basis for individualized clinical immunotherapy.