163例弥漫大B细胞淋巴瘤患者预后相关免疫表型研究  

Research of prognostic immunophenotypes in 163 patients of diffuse large B-cell lymphoma

作　　者：杨鑫 陈舒 祁昱 徐晓莹 管雪 杨亦宸 刘岩雪 郭玉虹[1,2] 巩文辰 高亚男 王先火 李维 李兰芳 付凯 张会来 孟斌 Yang Xin;Chen Shu;Qi Yu;Xu Xiaoying;Guan Xue;Yang Yichen;Liu Yanxue;Guo Yuhong;Gong Wenchen;Gao Yanan;Wang Xianhuo;Li Wei;Li Lanfang;Fu Kai;Zhang Huilai;Meng Bin(Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy,Tianjin Tianjin's Clinical Research Center of Cancer,Tianjin 300060,China;Department of Pathology,Tianjin Medical University Cancer Institute andHospital,Tianjin 300060,China;Department of Lymphoma,Tianjin Medical University Cancer Institute and Hospital,Tianjin 300060,China;Department of Pathology,Roswell Park Cancer Institute,Buffalo,New York,USA)

机构地区：[1]天津医科大学肿瘤医院,国家肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,天津市恶性肿瘤临床医学研究中心,天津医科大学肿瘤医院中美淋巴血液肿瘤诊治中心,300060 [2]天津医科大学肿瘤医院病理科,300060 [3]天津医科大学肿瘤医院淋巴瘤内科,300060 [4]天津医科大学肿瘤医院中美淋巴血液肿瘤诊治中心,美国罗斯威尔帕克癌症研究所病理科

出　　处：《中华血液学杂志》2021年第6期487-494,共8页Chinese Journal of Hematology

基　　金：国家自然科学基金(81700103)。

摘　　要：目的筛选并分析与弥漫大B细胞淋巴瘤(DLBCL)预后相关的免疫表型,探究其预后价值。方法选取天津医科大学肿瘤医院2011年1月至2016年12月收治的163例DLBCL患者,免疫组织化学染色检测DLBCL常见免疫表型,COX模型探索独立于国际预后指数(IPI)影响总生存(OS)与无进展生存(PFS)的免疫表型,并分析其两两联合表达对预后的影响。结果多因素分析显示BCL6阴性(PFS:HR=1.652,95%CI 1.030~2.649,P=0.037)、P53阳性(OS:HR=1.842,95%CI 1.008~3.367,P=0.047)、BCL2强阳性(OS:HR=2.102,95%CI 1.249~3.537,P=0.005;PFS:HR=2.126,95%CI 1.312~3.443,P=0.002)是DLBCL中独立于IPI的预后不良因素。亚组分析显示,在年龄≤60岁组患者中BCL6阴性(PFS:HR=2.042,95%CI 1.021~4.081,P=0.043)、P53阳性(OS:HR=3.069,95%CI 1.244~7.569,P=0.015)和BCL2强阳性(OS:HR=2.433,95%CI 1.165~5.082,P=0.018;PFS:HR=3.209,95%CI 1.606~6.410,P=0.001)对预后影响显著;在IPI 0~2分亚组患者中,BCL6阴性(OS:HR=2.467,95%CI 1.322~4.604,P=0.005;PFS:HR=2.248,95%CI 1.275~3.965,P=0.005)和BCL2强阳性(PFS:HR=2.045,95%CI 1.119~3.735,P=0.020)对预后影响显著。BCL6和BCL2强阳性的联合表达与DLBCL的预后相关(P=0.005和P<0.001),BCL6阳性/BCL2非强阳性(86例)预后最好[3年OS率(71.6±4.9)%,3年PFS率(67.0±5.1)%],BCL6阴性/BCL2强阳性(10例)预后最差[3年OS率(20.0±12.6)%,3年PFS率(10.0±9.5)%];BCL6、P53的联合表达与DLBCL的预后差异无统计学意义(P=0.061和P=0.089),但生存曲线显示BCL6阳性/P53阴性的病例(98例)预后较好[3年OS率(70.6±4.7)%,3年PFS率(64.6±4.9)%];BCL2强阳性、P53的联合表达与DLBCL的预后显著相关(P<0.001和P<0.001),BCL2强阳性/P53阳性的病例(5例)预后最差(3年OS率和PFS率均为0);无论BCL6与P53表达如何,BCL2强阳性的病例预后均比非强阳性病例差。结论BCL6阴性、P53阳性、BCL2强阳性三种免疫表型单独及联合表达对DLBCL尤其是年龄≤60岁和IPI 0~2分患者的预后预测具有一定价值。Objective To screen and analyze the prognostic protein biomarkers of DLBCL,and to explore their value in the prognostic evaluation.Methods 163 cases of confirmed DLBCLs from January 2011 to December 2016 were collected with their clinical,pathological and follow-up data,which were all from our hospital.The expression of protein markers were tested using immunohistochemical staining(IHC).The immune phenotypes independent of the International Prognostic Index(IPI)that affect overall survival(OS)and progression-free survival(PFS)of DLBCL were explored by COX regression model,and the effect of their co-expression on the prognosis were also analyzed.Result BCL6 negative(PFS:HR=1.652,95%CI 1.030-2.649,P=0.037),P53 positive(OS:HR=1.842,95%CI 1.008-3.367,P=0.047),and BCL2 strong positive expressions(S+)(OS:HR=2.102,95%CI 1.249-3.537,P=0.005;PFS:HR=2.126,95%CI 1.312-3.443,P=0.002)are adverse prognostic factors of DLBCL that are independent of IPI.BCL6-(PFS:HR=2.042,95%CI 1.021-4.081,P=0.043),P53+(OS:HR=3.069,95%CI 1.244-7.569,P=0.015)and BCL2S+(OS:HR=2.433,95%CI 1.165-5.082,P=0.018;PFS:HR=3.209,95%CI 1.606-6.410,P=0.001)are adverse prognostic factors in the group of age≤60-year-old;in the group of IPI score 0-2,cases with BCL6-(OS:HR=2.467,95%CI 1.322-4.604,P=0.005;PFS:HR=2.248,95%CI 1.275-3.965,P=0.005)and BCL2S+(PFS:HR=2.045,95%CI 1.119-3.735,P=0.020)have worse prognosis.The co-expression of BCL6-and BCL2S+has significant influence on prognosis of DLBCL(P=0.005 and P<0.001),in which BCL6+/non-BCL2S+(n=86)has the best prognosis[3-year-OS(71.6±4.9)%,3-year-PFS(67.0±5.1)%],and BCL6-/BCL2S+(n=10)has the worst prognosis[3-year-OS(20.0±12.6)%,3-year-PFS(10.0±9.5)%];the co-expression of BCL6-and P53+has no significant influence on prognosis(P=0.061 and P=0.089),however,those cases with BCL6+/P53-(n=98)often get better prognosis[3-year-OS(70.6±4.7)%,3-year-PFS(64.6±4.9)%]than others;the co-expression of P53+and BCL2S+has significant influence on prognosis of DLBCL(P<0.001 and P<0.001),and P53+/BCL2S+(n=5)has the worst p

关 键 词：弥漫大B细胞淋巴瘤 基因 BCL2 基因 P53 基因 BCL6 预后 

分 类 号：R733.1[医药卫生—肿瘤]