非特指型弥漫大B细胞淋巴瘤中PD-1、TIM-3、LAG-3与BTLA的表达水平及其对预后的影响

Expression of PD-1,TIM-3,LAG-3 and BTLA in diffuse large B-cell lymphoma and its effect on prognosis

目的:探讨非特指型弥漫大B细胞淋巴瘤(DLBCL)中程序性死亡蛋白1(PD-1)、T细胞免疫球蛋白黏蛋白分子3(TIM-3)、淋巴细胞激活基因3(LAG-3)及B和T淋巴细胞衰减器(BTLA)的表达水平及对预后的影响。方法:对郑州大学人民医院初诊的30例非特指型DLBCL患者的石蜡标本行免疫组织化学染色,分析上述分子单个阳性及共表达对无进展生存(PFS)期和总生存(OS)期的影响。结果:PD-1、TIM-3、LAG-3、BTLA单个阳性组与单个阴性组的预后差异均无统计学意义。PD-1、TIM-3共表达组及TIM-3、BTLA共表达组的中位PFS期分别是26和24个月,分别低于其非共表达组的54个月(P=0.021)和47个月(P=0.037);PD-1、TIM-3、LAG-3共表达组中位PFS期和OS期分别为17和25个月,显著低于非共表达组的41个月(P=0.024)和60个月(P=0.015);PD-1、TIM-3、LAG-3、BTLA共表达组中位PFS期和OS期分别是18和26个月,显著低于非共表达组的40个月(P=0.038)和57个月(P=0.041)。结论:非特指型DLBCL患者中PD-1、TIM-3共表达以及TIM-3、BTLA共表达者具有较短的PFS期,PD-1、TIM-3、LAG-3共表达者及PD-1、TIM-3、LAG-3、BTLA共表达者具有较短的PFS期和OS期。

Objective To investigate the expression levels of programmed death protein 1(PD-1)、T cell immunoglobulin domain and mucin domain 3(TIM-3)、lymphocyte activating gene 3(LAG-3)and B and T lymphocyte attenuator(BTLA)in Diffuse large B-cell lymphoma,not otherwise specified(DLBCL,NOS)and their effects on prognosis.Methods The paraffin specimens of 30 patients with DLBCL,NOS newly diagnosed in People′s Hospital of Zhengzhou University were stained with immunohistochemistry.The effects of single positive and co-expression of the above molecules on progression-free survival(PFS)phase and overall survival(OS)phase were analyzed.Results There was no significant difference in prognosis between PD-1,TIM-3,LAG3,BTLA single positive group and single negative group.The median PFS phase of PD-1 and TIM-3 co-expression group and TIM3 and BTLA co-expression group were 26 and 24 months respectively,which were both lower than the 54 months(P=0.021)and 47 months(P=0.037)in non-co-expression group.The median PFS phase and OS phase of PD-1,TIM-3 and LAG-3 co-expression group were 17 and 25 months respectively,which were significantly lower than the 41 months(P=0.024)and 60 months(P=0.015)of non-co-expression group.The median PFS phase and OS phase of PD-1,TIM-3,LAG-3 and BTLA co-expression group were 18 and 26 months respectively,which were significantly lower than the 40 months(P=0.038)and 57 months(P=0.041)of non-co-expression group.Conclusions In patients with DLBCL,NOS,those with PD-1 and TIM-3 co-expression as well as those with TIM-3 and BTLA co-expression have poor PFS phase.Patients with PD-1,TIM-3 and LAG-3 co-expression and patients with PD-1,TIM-3,LAG-3 and BTLA co-expression have poor PFS and OS phase.