A20基因缺失对弥漫大B细胞淋巴瘤临床病理特征和预后的影响及相关分子机制研究

发布时间：2018-02-02 09:42

本文关键词： 淋巴瘤 A基因 NF-κB Survivin 预后基因缺失　出处：《重庆医学》2017年19期 　论文类型：期刊论文

【摘要】：目的检测弥漫大B细胞淋巴瘤(DLBCL)中肿瘤坏死因子α诱导蛋白3基因(A20基因)缺失情况,探讨A20基因缺失对DLBCL临床过程及预后的影响及其与核因子-κB(NF-κB)通路活化的关系。方法荧光原位杂交检测其A20基因缺失情况;免疫组织化学染色检测肿瘤中A20、Survivin、P65、Ki-67蛋白的表达,TUNEL技术检测肿瘤细胞凋亡水平,收集临床病理资料并随访,进行统计分析。结果 DLBCL病例A20基因缺失率为21.7%,活化后B细胞样型(ABC)-DLBCL的A20基因缺失率明显高于生发中心B细胞样型(GCB)-DLBCL(30.6%vs.8.3%,P0.05),A20蛋白表达与A20基因缺失呈负相关(r=-0.259,P=0.023),P65蛋白和Survivin蛋白表达与A20基因缺失呈正相关(r=0.280、0.313,P=0.015、0.007);肿瘤细胞凋亡在A20基因缺失的DLBCL病例中较低,在A20蛋白表达阳性病例中明显高于表达阴性病例,在Survivin和P65蛋白阳性表达病例中明显低于阴性表达病例(P0.05),而在ABC-DLBCL和GCB-DLBCL病例间差异无统计学意义(P0.05);COX回归分析结果显示,年龄、A20基因的缺失、DLBCL类型和Ki67表达是DLBCL独立的生存相关因素;A20基因缺失者的生存状况明显较未缺失者差(P=0.015)。结论 A20缺失可能影响A20蛋白表达,使其对NF-κB活化的负调节作用减弱,使Survivin表达上调而影响肿瘤细胞的增殖和凋亡;A20基因缺失对DLBCL的临床过程和预后有一定影响。
[Abstract]:Objective to detect the deletion of tumor necrosis factor- 伪 inducible protein 3 gene (TNF- 伪 -inducible protein 3 gene) in DLBCLs of diffuse large B-cell lymphoma (DLBCLs). To investigate the effect of A20 gene deletion on the clinical process and prognosis of DLBCL and its relationship with the activation of nuclear factor- 魏 B (NF- 魏 B) NF- 魏 B.Methods the deletion of A20 gene was detected by fluorescence in situ hybridization. Immunohistochemical staining was used to detect the expression of survivin P65 Ki-67 protein in tumor cells and Tunel technique was used to detect the apoptosis level of tumor cells. Clinical and pathological data were collected and followed up for statistical analysis. Results the deletion rate of A20 gene in DLBCL patients was 21.7%. The deletion rate of A20 gene was significantly higher in activated B cell like type B cell like type B cell type than in germinal center B cell like type B cell type, GCB-DLBCLC 30.6vs.8.3%. There was a negative correlation between the expression of P0.05A20 protein and the deletion of A20 gene (P 0.023). There was a positive correlation between the expression of p65 protein and Survivin protein and the deletion of A20 gene. Tumor cell apoptosis was lower in DLBCL patients with A20 gene deletion and higher in A20 protein positive cases than in A20 negative cases. The positive expression of Survivin and p65 protein was significantly lower than that of negative expression cases (P0.05). However, there was no significant difference between ABC-DLBCL and GCB-DLBCL cases (P 0.05). COX regression analysis showed that the type of DLBCL and the expression of Ki67 were independent survival factors of DLBCL. Conclusion A20 deletion may affect the expression of A20 protein and weaken the negative regulation of NF- 魏 B activation. The expression of Survivin was up-regulated, which affected the proliferation and apoptosis of tumor cells. The deletion of A 20 gene may affect the clinical process and prognosis of DLBCL.
【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】：国家自然科学基金资助项目(NO.81160299)
【分类号】：R733.1
【正文快照】： 弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DL-BCL)是成人淋巴瘤中最常见的一种类型,约占非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL)的30%[1],在我国已达45.8%[2]。它可发生于任何年龄,以中老年人最为常见,中位发病年龄60~64岁。根据肿瘤细胞的基因表达谱,非特指的DLB

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