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%,P<0.05),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(P<0.05),而在ABC-DLBCL和GCB-DLBCL病例间差异无统计学意义(P>0.05);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。
Objective To detect the A20 gene deletion,investigate the impacts of A20 gene deletion on clinicopathological features and prognosis of DLBCL, and relationship between activation of NF-κB pathway and relative molecular pathogenesis. Meth- ods A20 gene deletion was detected by fluorescence in situ hybridization （FISH）. The expression of A20,Survivin,P65 and Ki-67 were detected by immunohistochemistry stain. Apoptosis was assayed by TUNEL. Follow-up and statistical analysis were done. Re- suits The deletion rate of A20 gene was 21.7%. The deletion rate of A20 gene was obviously higher in ABC-like DLBCL than that in GCB-like DLBCL （30.6% vs. 8.3% ,P〈O. 05）. It was observed that there was a negative correlation between A20 protein ex- pression and A20 gene deletion （r=-0. 259 ,P=0. 023）. The expression of P65 and Survivin protein was positively correlated with the A20 gene deletion （r= 0. 280, P = 0. 015 ; r= 0. 313, P = 0. 007）. Apoptosis rate was significantly reduced in DLBCL patients with A20 gene deletion. The apoptosis rate was higher in cases with positive expression of A20 protein,while that was lower in ca- ses with positive expression of p65 and Survivin protein than those with negative expression of corresponding protein. There was no statistically significant difference in apoptosis rate between ABC-like and GCB-like DLBCL patients （P~〉0.05）. COX regression a- naiysis indicated that age, A20 gene deletion, types of DLBCL and Ki67 expression were independent factors associated with survival status. Log-rank test showed that there was a statistical difference in survival status between the cases with and without A20 gene deletion （P=0. 015）. Conclusion A20 gene deletion may associate with the attenuation of A20 protein expression. The latter weak- ens negative feedback regulation of A20 protein for NF-κB pathway. An up-regulated expression of Survivin and abnormal prolifera- tion and apoptosis may be result from the abnormal activation of NF-κB. A20 gene deletion brings certain influence on clinical course and prognosis of DLBCL.
出处
《重庆医学》
CAS
北大核心
2017年第19期2594-2598,共5页
Chongqing medicine
基金
国家自然科学基金资助项目(NO.81160299)
