Activation of the NF-kappa B Pathway and Heterozygous Deletion of TNFAIP3 (A20) Confer Superior Survival in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type
Activation of the NF-kappa B Pathway and Heterozygous Deletion of TNFAIP3 (A20) Confer Superior Survival in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type
复制标题
NF-kappa B 通路的激活和 TNFAIP3 (A20) 的杂合缺失可提高鼻型结外自然杀伤/T 细胞淋巴瘤的生存率
DOI：
10.1093/ajcp/aqz041
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发表时间：
2019
影响因子：
3.5
通讯作者：
Yan Qing-Guo
中科院分区：
文献类型：
--
作者：
Liu Fang;Zheng Jun-Ping;Wang Lu;Zhao Dan-Hui;Li Ming-Yang;Wang Ying-Mei;Liu Yang;Ma Jing;Zeng Nai-Yan;Liu Hong-Xiang;Liang Rong;Guo Shuang-Ping;Wang Zhe;Yan Qing-Guo
目的探讨TNFAIP 3缺失和NF-κB活化在鼻型结源性自然杀伤/T细胞淋巴瘤（ENKTCL）中的作用。采用免疫组化法检测NF-κB通路的活化和TNFAIP 3（A20）的表达，用FICTION分析TNFAIP 3的缺失（荧光免疫分型和间期细胞遗传学作为研究肿瘤的工具）、使用桑格测序检测突变和使用甲基化特异性测序检测启动子甲基化。结果在31.2%的病例（43/138）中观察到NF-κB通路活化，15.2%（21/138）的乳腺癌组织TNFAIP 3表达阴性，35%（35/100）的乳腺癌组织TNFAIP 3存在异源性缺失，未发现TNFAIP 3第2 ~ 9外显子突变和启动子甲基化。Kaplan-Meier分析显示NF-κB通路激活或TNFAIP 3杂合性缺失的患者具有较上级的总生存期。
ObjectivesTo investigate the role ofTNFAIP3deletions and NF-κB activation in extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type.MethodsIn total, 138 patients with ENKTCL were included. Activation of NF-κB pathway and expression of TNFAIP3 (A20) were examined by immunohistochemistry.TNFAIP3was analyzed for deletions using FICTION (fluorescence immunophenotyping and interphase cytogenetics as a tool for investigating neoplasms), for mutations using Sanger sequencing, and for promoter methylation using methylation-specific sequencing.ResultsNF-κB pathway activation was observed in 31.2% of cases (43/138),TNFAIP3expression was negative in 15.2% of cases (21/138), and heterozygousTNFAIP3deletion was observed in 35% of cases (35/100).TNFAIP3exons 2 to 9 mutations and promoter methylation were not observed. Kaplan-Meier analysis showed patients with NF-κB pathway activation orTNFAIP3heterozygous deletion to have a longer overall survival.ConclusionsOur study demonstrated that NF-κB activation andTNFAIP3heterozygous deletion confer superior survival in patients with ENKTCL.