摘要
目的弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)是成人淋巴瘤中最常见的非霍奇金淋巴瘤(non-hodgkin lymphoma,NHL),近年来发病有上升趋势,治疗效果一直不佳。本研究检测DLBCL中A20(tumor necrosis factor alpha-induced protein 3gene,TNFAIP3,A20gene)基因缺失情况,探讨A20基因缺失对DLBCL中核因子-κB(nuclear factor-kappaB,NF-κB)通路活化和P-gp表达的影响。方法收集2009-06-01-2015-05-31贵州医科大学附属医院病理科60例DLBCL标本,以同期12例淋巴结反应性增生病例作研究对照。采用荧光原位杂交检测A20探针在60例DLBCL和12例淋巴结反应性增生病例中DNA缺失的情况。免疫组织化PV两步法检测A20、p65、P-gp蛋白的表达,收集临床病理资料并随访。结果 DLBCL病例中A20基因缺失率为21.7%(13/60),淋巴结反应性增生病例中未检出A20基因缺失;在DLBCL病例中活化B细胞样(Activated B cell-like,ABC)的A20基因缺失率30.5%明显高于生发中心B细胞样(germinal center B cell-like,GCB)的8.3%,χ~2=4.190,P=0.041。A20蛋白表达与A20基因缺失之间呈低度负相关(r=-0.259,P=0.023),p65蛋白和P-gp蛋白表达与A20基因缺失之间呈低度正相关(r=0.280,P=0.015;r=0.278,P=0.020)。P-gp在DLBCL阳性表达率48.3%(29/60),在淋巴结反应性增生中表达率为16.7%(2/12),χ~2=4.090,P=0.043。DLBCL中ABC-DLBCL的P-gp蛋白的表达阳性率61.1%明显高于GCB-DLBCL的29.1%,χ~2=5.032,P=0.015。结论 DLBCL中A20的缺失和蛋白表达的下调可能降低了A20对NF-κB的负调节作用,使肿瘤内NF-κB异常活化,下游靶基因MDR1转录上调,P-gp表达增加,使肿瘤细胞对DLBCL的化疗产生耐药。
OBJECTIVE Diffuse large B cell lymphoma is the most common non Hodgkin lymphoma in adults＇ lymphoma,there is an upward trend in the treatment in recent years and the effect of treatment has been poor.This study aims to detect the deletion of the A20 gene in diffuse large B cell lymphoma,investigate the effect of A20 gene deletion on diffuse large B cell lymphoma NF-κB pathway activation and expression of P-gp and its related mechanism.METHODS A total of 60 cases with DLBCL were collected from the Department of Pathology of the Affiliated Hospital of Guizhou Medical University from June 1,2009 to May 31,2015 and a total of 12 cases with lymph node reactive hyperplasia were used as controls in this study.Fluorescence in situ hybridization probe was used to detect A20 DNA deletion in 60 cases diffuse large B cell lymphoma and 12 cases lymph node reactive hyperplasia;The expression of A20,p65 and P-gp protein were detected by immunohistochemistry stain and the clinical data was collected and followed up.RESULTS 1.The deletion rate of A20 gene was 21.7%（13/60）.A20 gene deletion wasn＇t found in 12 cases of reactive proliferation.The deletion of A20 in ABC-like DLBCL was obviously higher than in GCB-like DLBCL（30.5%：8.3%）（χ^2=4.190,P=0.041）.It was observed that the litter negative correlation between A20 protein expression and A20 gene deletion（r=-0.259,P=0.023）.p65 protein and P-gp protein expression was positively correlated with A20 gene deletion（r=0.280,P=0.015;r=0.278,P=0.020）;2.P-gp in DLBCL positive expression rate was 48.3%（29/60）,in the reactive hyperplasia of lymph node expression rate was 16.7%（2/12）（χ^2=4.090,P=0.043）,the positive expression rate of P-gp protein in ABC-DLBCL is higher than that of GCB-DLBCL（61.1% ∶29.1%）（χ^2=5.032,P=0.015）.CONCLUSIONS The deletion of A20 and the down-regulation of A20 protein expression in DLBCL may decrease the negative regulation effect of A20 on NF-κB,abnormal activation of NF-κB in tumor,upregulation of MDR1 transcrip
出处
《中华肿瘤防治杂志》
CAS
北大核心
2017年第11期750-754,共5页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(81160299)
