A20基因缺失对弥漫大B细胞淋巴瘤P-gp表达影响

发布时间：2018-07-04 14:23

本文选题：弥漫大B细胞淋巴瘤 + A　；参考：《中华肿瘤防治杂志》2017年11期

【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。
[Abstract]:Objective diffuse large B cell lymphoma (diffuse large B cell lymphoma) is the most common non-Hodgkin 's lymphoma in adults. In this study, we examined the deletion of A20 (tumor necrosis factor alpha-induced protein 3gene TNFAIP3mA20 gene in DLBCL, and investigated the effect of A20 gene deletion on the activation of nuclear factor-kappa BNF- 魏 B pathway and the expression of P-gp in DLBCL. Methods 60 DLBCL specimens were collected from Department of Pathology, affiliated Hospital of Guizhou Medical University, 2009-06-01-2015-05-31, and 12 cases of reactive lymphadenopathy were used as control group. The DNA deletions of A20 probe in 60 cases of DLBCL and 12 cases of reactive lymphadenopathy were detected by fluorescence in situ hybridization. Immunohistochemical PV two-step method was used to detect the expression of P-GP protein in A20 p65. The clinicopathological data were collected and followed-up. Results the deletion rate of A20 gene was 21.7% (13 / 60) in DLBCL patients, and no A20 gene deletion was detected in patients with reactive lymphadenopathy. The deletion rate of A20 gene in Activated B cell-like Activated was significantly higher than that of (germinal center B cell-like GCB in germinal center. There was a low negative correlation between the expression of P0.041.A20 protein and the deletion of A20 gene (r-0.259P0.023) p65 protein and P-gp protein expression and A20 gene deletion. The positive expression rate of P-gp was 48.3% (29 / 60) in DLBCL, 16.7% (2 / 12) in reactive lymphadenopathy, 61.1% in ABC-DLBCL was significantly higher than that in GCB-DLBCL (61.1%). Conclusion the deletion of A20 and the down-regulation of protein expression in DLBCL may decrease the negative regulation of A20 on NF- 魏 B, activate NF- 魏 B abnormally, and up-regulate the expression of P-gp in the downstream target gene MDR1, which may result in drug resistance of tumor cells to DLBCL chemotherapy.
【作者单位】：贵州医科大学病理学教研室;贵州医科大学附属医院病理科;
【基金】：国家自然科学基金(81160299)
【分类号】：R733.1

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