外周血sPD-L1在预测侵袭性非霍奇金淋巴瘤患者预后中的临床价值
|
摘要
目的探讨外周血可溶性程序性细胞死亡配体(s PD-L1)在预测侵袭性非霍奇金淋巴瘤(NHL)患者预后中的应用价值。方法收集112例侵袭性NHL[弥漫大B细胞淋巴瘤(DLBCL)]患者的临床资料,并选择同期来医院体检的40例正常健康人作为对照组。所有对象均采集空腹外周血标本,采用双抗体夹心-酶联免疫吸附法(ABC-ELISA)测定外周血s PD-L1水平,分析其与DLBCL临床病理参数及预后的关系。结果病例组外周血s PD-L1水平高于对照组(P <0. 05)。NHL国际预后指数(IPI)为高危、Ann Arbor分期为Ⅲ~Ⅳ期、肿块大小≥10 cm、病理类型为T细胞型、治疗反应为SD+PD的患者血清s PD-L1水平高于IPI指数为低危、Ann Arbor分期为Ⅰ~Ⅱ期、肿块大小<10 cm、病理类型为B细胞型、治疗反应为CR+PR的患者(P <0. 05)。高s PD-L1患者生存率(OS)明显低于低s PD-L1患者(P <0. 05)。Cox分析显示:高s PD-L1、Ann Arbor为Ⅲ~Ⅳ期、病理类型为T细胞型均为导致DLBCL患者预后不良的独立危险因素(P <0. 05)。结论 DLBCL患者外周血s PD-L1呈明显高表达,且其表达水平的变化与患者IPI指数、临床分期、肿块大小、病理类型、治疗反应均存在紧密联系,同时也是影响患者预后的危险因素。
Objective To investigate the value of soluble programmed cell death ligand( s PD-L1) in predicting the prognosis of invasive non-Hodgkin's lymphoma( NHL). Methods The clinical data of 112 patients with invasive NHL [diffused large B cell lymphoma( DLBCL) ] who were admitted to the hospital during the period from January 2013 to January 2017 were collected. 40 normal healthy people who received physical examination in the hospital during the same period were selected as the control group. Fasting peripheral blood samples were collected from all subjects to determine the level of s PD-L1 by double antibody sandwich-enzyme-linked immunosorbent assay( ABC-ELISA). Its relationship with clinicopathological parameters and prognosis of DLBCL was analyzed. Results The level of s PD-L1 in peripheral blood was higher in the case group than in the control group( P <0. 05). The level of s PD-L1 in peripheral blood was higher in patients with NHL international prognosis index( IPI) of high risk,at Ann Arbor stage Ⅲ ~ Ⅳ,with tumors ≥10 cm,pathological type of T cell type and with treatment response of SD + PD than in patients with IPI of low risk,at Ann Arbor stage Ⅰ ~ Ⅱ,with tumors < 10 cm,pathological type of B-cell type and with treatment response of CR + PR( P < 0. 05). The survival rate( OS) of patients with high s PD-L1 was significantly lower than that of patients with low s PD-L1( P < 0. 05). Cox analysis showed that high s PD-L1,Ann Arbor stage Ⅲ ~ Ⅳ and pathological types of T cell type were independent risk factors for poor prognosis of patients with DLBCL( P < 0. 05). Conclusion The expression of s PD-L1 in peripheral blood of patients with DLBCL is significantly higher,and changes in the expression level of s PD-L1 are closely related to the patient's IPI,clinical stage,tumor size,pathological type and response to treatment. They also are risk factors for the prognosis of patients.
Objective To investigate the value of soluble programmed cell death ligand( s PD-L1) in predicting the prognosis of invasive non-Hodgkin's lymphoma( NHL). Methods The clinical data of 112 patients with invasive NHL [diffused large B cell lymphoma( DLBCL) ] who were admitted to the hospital during the period from January 2013 to January 2017 were collected. 40 normal healthy people who received physical examination in the hospital during the same period were selected as the control group. Fasting peripheral blood samples were collected from all subjects to determine the level of s PD-L1 by double antibody sandwich-enzyme-linked immunosorbent assay( ABC-ELISA). Its relationship with clinicopathological parameters and prognosis of DLBCL was analyzed. Results The level of s PD-L1 in peripheral blood was higher in the case group than in the control group( P <0. 05). The level of s PD-L1 in peripheral blood was higher in patients with NHL international prognosis index( IPI) of high risk,at Ann Arbor stage Ⅲ ~ Ⅳ,with tumors ≥10 cm,pathological type of T cell type and with treatment response of SD + PD than in patients with IPI of low risk,at Ann Arbor stage Ⅰ ~ Ⅱ,with tumors < 10 cm,pathological type of B-cell type and with treatment response of CR + PR( P < 0. 05). The survival rate( OS) of patients with high s PD-L1 was significantly lower than that of patients with low s PD-L1( P < 0. 05). Cox analysis showed that high s PD-L1,Ann Arbor stage Ⅲ ~ Ⅳ and pathological types of T cell type were independent risk factors for poor prognosis of patients with DLBCL( P < 0. 05). Conclusion The expression of s PD-L1 in peripheral blood of patients with DLBCL is significantly higher,and changes in the expression level of s PD-L1 are closely related to the patient's IPI,clinical stage,tumor size,pathological type and response to treatment. They also are risk factors for the prognosis of patients.
引文
[1]Zhou J,Tiemann K,Chomchan P,et al.Dual functional BAFF receptor aptamers inhibit ligand-induced proliferation and deliver siRNAs to NHL cells[J].Nuc Acid Res,2013,41(7):4266-4283.
[2]马芹,张会来,王华庆,等.外周血淋巴细胞绝对数对弥漫大B细胞淋巴瘤患者预后价值的临床分析[J].中国肿瘤临床,2014,41(8):503-507.
[3]Paydas S,Ba4Ir E,Seydaoglu G,et al.Programmed death-1(PD-1),programmed death-ligand 1(PD-L1),and EBV-encoded RNA(EBER)expression in Hodgkin lymphoma[J].Annals Hematol,2015,94(9):1545-1552.
[4]陈琳,尹青松,魏旭东,等.弥漫大B细胞淋巴瘤患者化疗前后外周血细胞T-bet和GATA-3基因转录水平的变化[J].中华血液学杂志,2013,34(11):967-969.
[5]马丛丛,刘彦琴.非霍奇金淋巴瘤患者外周血25-羟维生素D_3水平及临床意义[J].中国实验血液学杂志,2015,23(2):431-434.
[6]Bertsias GK,Nakou M,Choulaki C,et al.Genetic,immunologic,and immunohistochemical analysis of the programmed death 1/programmed death ligand 1 pathway in human systemic lupus erythematosus[J].Arthritis Res Ther,2014,60(1):207-218.
[7]丁士华,熊述道,翟志敏,等.非霍奇金淋巴瘤患者外周血及骨髓中免疫球蛋白、T细胞受体基因重排检测的意义[J].山东医药,2015,55(5):34-36.
[8]勇威本.非霍奇金淋巴瘤WHO(1997)分类若干新亚型的生物学与临床特征[J].中华血液学杂志,2003,24(10):558-560.
[9]石远凯.美国国家癌症综合网非霍奇金淋巴瘤治疗指南2008年第二版介绍[J].中华肿瘤杂志,2008,30(8):638-640.
[10]杨学宁,吴一龙.实体瘤治疗疗效评价标准-RECIST[J].循证医学,2004,4(2):85-90.
[11]Lee JJ,Chan A,Tang T.Tuberculosis reactivation in a patient receiving anti-programmed death-1(PD-1)inhibitor for relapsed Hodgkin's lymphoma[J].Acta Oncologica,2016,55(4):519-520.
[12]Chong LC,Twa DD,Mottok A,et al.Comprehensive characterization of programmed death ligand structural rearrangements in B-cell non-Hodgkin lymphomas[J].Blood,2016,128(9):1206-1213.
[13]陈泽,蔡志梅,赵利东,等.BCL-2与PD-L1联合检测在预测初治急性白血病预后中的价值分析[J].中国实验血液学杂志,2017,25(6):1636-1640.
[14]赵越,卜庆.PD-L1和PD-1在外周T细胞淋巴瘤中的表达及临床意义[J].天津医药,2016,44(3):349-352.
[15]王先火,傅凯,潘嫱,等.PD-1/PD-L1轴与淋巴瘤[J].中华微生物学和免疫学杂志,2017,37(5):400-404.
[16]董玲,吕慧娟,孔令喆,等.PD-1/PD-L1通路在恶性淋巴瘤中的研究进展[J].中华微生物学和免疫学杂志,2015,35(10):789-792.
[17]Villasboas JC,Ansell S.Checkpoint inhibition:programmed cell death 1 and programmed cell death 1 ligand inhibitors in hodgkin lymphoma[J].Cancer J,2016,22(1):17-22.
[2]马芹,张会来,王华庆,等.外周血淋巴细胞绝对数对弥漫大B细胞淋巴瘤患者预后价值的临床分析[J].中国肿瘤临床,2014,41(8):503-507.
[3]Paydas S,Ba4Ir E,Seydaoglu G,et al.Programmed death-1(PD-1),programmed death-ligand 1(PD-L1),and EBV-encoded RNA(EBER)expression in Hodgkin lymphoma[J].Annals Hematol,2015,94(9):1545-1552.
[4]陈琳,尹青松,魏旭东,等.弥漫大B细胞淋巴瘤患者化疗前后外周血细胞T-bet和GATA-3基因转录水平的变化[J].中华血液学杂志,2013,34(11):967-969.
[5]马丛丛,刘彦琴.非霍奇金淋巴瘤患者外周血25-羟维生素D_3水平及临床意义[J].中国实验血液学杂志,2015,23(2):431-434.
[6]Bertsias GK,Nakou M,Choulaki C,et al.Genetic,immunologic,and immunohistochemical analysis of the programmed death 1/programmed death ligand 1 pathway in human systemic lupus erythematosus[J].Arthritis Res Ther,2014,60(1):207-218.
[7]丁士华,熊述道,翟志敏,等.非霍奇金淋巴瘤患者外周血及骨髓中免疫球蛋白、T细胞受体基因重排检测的意义[J].山东医药,2015,55(5):34-36.
[8]勇威本.非霍奇金淋巴瘤WHO(1997)分类若干新亚型的生物学与临床特征[J].中华血液学杂志,2003,24(10):558-560.
[9]石远凯.美国国家癌症综合网非霍奇金淋巴瘤治疗指南2008年第二版介绍[J].中华肿瘤杂志,2008,30(8):638-640.
[10]杨学宁,吴一龙.实体瘤治疗疗效评价标准-RECIST[J].循证医学,2004,4(2):85-90.
[11]Lee JJ,Chan A,Tang T.Tuberculosis reactivation in a patient receiving anti-programmed death-1(PD-1)inhibitor for relapsed Hodgkin's lymphoma[J].Acta Oncologica,2016,55(4):519-520.
[12]Chong LC,Twa DD,Mottok A,et al.Comprehensive characterization of programmed death ligand structural rearrangements in B-cell non-Hodgkin lymphomas[J].Blood,2016,128(9):1206-1213.
[13]陈泽,蔡志梅,赵利东,等.BCL-2与PD-L1联合检测在预测初治急性白血病预后中的价值分析[J].中国实验血液学杂志,2017,25(6):1636-1640.
[14]赵越,卜庆.PD-L1和PD-1在外周T细胞淋巴瘤中的表达及临床意义[J].天津医药,2016,44(3):349-352.
[15]王先火,傅凯,潘嫱,等.PD-1/PD-L1轴与淋巴瘤[J].中华微生物学和免疫学杂志,2017,37(5):400-404.
[16]董玲,吕慧娟,孔令喆,等.PD-1/PD-L1通路在恶性淋巴瘤中的研究进展[J].中华微生物学和免疫学杂志,2015,35(10):789-792.
[17]Villasboas JC,Ansell S.Checkpoint inhibition:programmed cell death 1 and programmed cell death 1 ligand inhibitors in hodgkin lymphoma[J].Cancer J,2016,22(1):17-22.