Fbxw7蛋白在弥漫大B细胞淋巴瘤中的表达及其临床意义  

Expression of Fbxw7 protein in diffuse large B-cell lymphoma and its clinical significance

作　　者：刘梦玉 王万里[1] 郭淑利[1] 王慧睿[1] 李玉富 Liu Mengyu;Wang Wanli;Guo Shuli;Wang Huirui;Li Yufu(Department of Hematology,Luoyang Central Hospital Affiliated to Zhengzhou University,Zhengzhou 471000,China;Department of Hematology,Cancer Hospital Affiliated to Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学附属洛阳市中心医院血液内科,471000 [2]郑州大学附属肿瘤医院血液科,450000

出　　处：《白血病．淋巴瘤》2020年第6期340-345,共6页Journal of Leukemia & Lymphoma

摘　　要：目的探讨弥漫大B细胞淋巴瘤(DLBCL)中Fbxw7蛋白的表达及其临床意义,为DLBCL预后判断和寻找新的治疗靶点提供依据。方法选择2011年1月至2017年9月郑州大学附属肿瘤医院收治的已行免疫组织化学检测c-myc蛋白的72例初治DLBCL患者,收集淋巴结活组织检查后的石蜡包埋标本及患者临床资料,同时选取22例淋巴结反应性增生组织标本作为对照。采用免疫组织化学方法检测DLBCL组织和对照组织中Fbxw7蛋白的表达。分析Fbxw7蛋白和c-myc蛋白表达的关系、Fbxw7蛋白表达与DLBCL患者临床病理特征、疗效及预后的关系。结果Fbxw7蛋白在DLBCL组织中的阳性率低于对照组织[63.89%(46/72)比86.36%(19/22)],差异有统计学意义(χ^2=3.990,P=0.046)。DLBCL患者中,非生发中心B细胞(non-GCB)组的Fbxw7蛋白阳性率低于生发中心B细胞(GCB)组[48.15%(13/27)比73.33%(33/45)],差异有统计学意义(χ^2=4.639,P=0.031);不同年龄、性别、肿瘤分期、国际预后指数(IPI)评分、B症状、美国东部肿瘤协作组(ECOG)评分、乳酸脱氢酶水平、β2微球蛋白水平以及初始治疗后疗效的患者间Fbxw7蛋白阳性率差异均无统计学意义(均P>0.05)。在DLBCL组织中,Fbxw7与c-myc蛋白的表达呈负相关(r=-0.255,P=0.031)。Fbxw7阳性组的3年总生存率、3年无进展生存率均高于Fbxw7阴性组(88.3%比70.2%,82.0%比60.1%,均P<0.05)。Cox多因素分析显示,Fbxw7蛋白表达下调是影响DLBCL患者OS和PFS的独立危险因素(HR=3.656,95%CI 1.055~12.674,P=0.041;HR=2.897,95%CI 1.092~7.688,P=0.033)。结论DLBCL患者Fbxw7蛋白与c-myc蛋白的表达呈负相关,在DLBCL中Fbxw7蛋白表达下调,并且在non-GCB亚型中下调更为明显。Fbxw7蛋白表达下调与DLBCL的不良预后相关,Fbxw7可能成为DLBCL新的治疗靶点。Objective To explore the expression of Fbxw7 protein and its clinical significance in diffuse large B-cell lymphoma(DLBCL),and to provide a basis for prognostic judgement and searching the new therapeutic targets of DLBCL.Methods A total of 72 patients with newly diagnosed DLBCL who received immunohistochemical detection of c-myc protein from January 2011 to September 2017 in Cancer Hospital Affilicoted to Zhengzhou University were enrolled.The paraffin-embedded specimens after lymph node biopsy and the clinical data of patients were also collected.At the same time,22 samples of lymph node reactive hyperplasia were selected as the control group.Immunohistochemical method was used to detect the expression of Fbxw7 protein in DLBCL tissues and control tissues.The relationship between the expression of Fbxw7 protein and c-myc protein,the association of Fbxw7 protein expression with DLBCL patients'clinicopathological characteristics,efficacy and prognosis were analyzed.Results The positive rate of Fbxw7 protein in DLBCL tissues was lower than that in control tissues,and the difference was statistically significant[63.89%(46/72)vs.86.36%(19/22),χ^2=3.990,P=0.046].Among DLBCL patients,the positive rate of Fbxw7 protein in non-germinal center B cell(non-GCB)group was lower than that in germinal center B cell(GCB)group,and the difference was statistically significant[48.15%(13/27)vs.73.33%(33/45),χ^2=4.639,P=0.031].There were no statistically significant differences in the positive rate of Fbxw7 protein among patients with different age,gender,neoplasm staging,international prognostic index(IPI)scores,B symptom,Eastern Cooperative Oncology Group(ECOG)score,lactate dehydrogenase(LDH)level,β2 microglobulin level,and therapeutic efficacy after initial treatment(all P>0.05).In DLBCL tissues,the expression of Fbxw7 and c-myc protein was negatively correlated(r=-0.255,P=0.031).The 3-year overall survival(OS)rate and 3-year progression-free survival(PFS)rate(88.3%and 82.0%)of the Fbxw7 positive group were higher than those o

关 键 词：淋巴瘤 大B-细胞 弥漫性 原癌基因蛋白质类 Fbxw7蛋白 C-MYC蛋白 免疫组织化学 预后 

分 类 号：R733.1[医药卫生—肿瘤]