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TNFAIP8的过表达与浸润性导管癌患者的肿瘤侵袭性及不良预后相关。

Overexpression of TNFAIP8 is associated with tumor aggressiveness and poor prognosis in patients with invasive ductal breast carcinoma.

作者信息

Xiao Min, Xu QingYong, Lou Chun, Qin Yu, Ning XiaoMing, Liu TianBo, Zhao XuHai, Jia ShuSheng, Huang YuanXi

机构信息

Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China.

Department of Breast Radiotherapy, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, China.

出版信息

Hum Pathol. 2017 Apr;62:40-49. doi: 10.1016/j.humpath.2016.12.020. Epub 2017 Jan 10.

Abstract

Tumor necrosis factor α-induced protein 8 (TNFAIP8), a transcription factor nuclear factor κB-inducible, antiapoptotic and oncogenic molecule, is associated with prognosis of several human malignancies. However, the relationship between TNFAIP8 and the prognosis of the invasive ductal carcinoma (IDC) of the breast remains unclear. TNFAIP8 expression was evaluated using real-time polymerase chain reaction (PCR) and Western blot analysis in 20 fresh IDC tissues and immunohistochemical analysis in 351 paraffin-embedded IDC tissues. Real-time PCR and Western blot analysis demonstrated that both TNFAIP8 messenger RNA and protein were up-regulated in IDC tissues compared with the paired adjacent noncancerous tissues. Immunohistochemistry revealed that TNFAIP8 expression was significantly correlated with some clinicopathological factors, including axillary lymph node metastasis (P=.001), advanced TNM stage (P<.001), high histologic grade (P<.001), molecular subtype (P<.001), and postoperative recurrence (P<.001). Univariate and multivariate logistic regression analyses demonstrated that TNFAIP8 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 1.818; 95% confidence interval, 1.167-2.832; P=.008). Moreover, Kaplan-Meier analysis indicated that IDC patients with high TNFAIP8 expression had a shorter survival time than did those with low TNFAIP8 expression, and multivariate analysis indicated that TNFAIP8 was an independent prognostic factor for overall survival and disease-free survival in IDC (P=.041 and P=.020, respectively). Therefore, TNFAIP8 overexpression may contribute to tumor progression, and it may be a novel prognostic biomarker for the patients with IDC.

摘要

肿瘤坏死因子α诱导蛋白8(TNFAIP8)是一种转录因子,可诱导核因子κB,具有抗凋亡和致癌作用,与多种人类恶性肿瘤的预后相关。然而,TNFAIP8与乳腺浸润性导管癌(IDC)预后之间的关系仍不清楚。采用实时聚合酶链反应(PCR)和蛋白质免疫印迹分析评估了20例新鲜IDC组织中TNFAIP8的表达,并采用免疫组织化学分析评估了351例石蜡包埋的IDC组织中TNFAIP8的表达。实时PCR和蛋白质免疫印迹分析表明,与配对的相邻非癌组织相比,TNFAIP8信使核糖核酸和蛋白质在IDC组织中均上调。免疫组织化学显示,TNFAIP8表达与一些临床病理因素显著相关,包括腋窝淋巴结转移(P = 0.001)、TNM晚期(P < 0.001)、高组织学分级(P < 0.001)、分子亚型(P < 0.001)和术后复发(P < 0.001)。单因素和多因素逻辑回归分析表明,TNFAIP8过表达与腋窝淋巴结转移密切相关(比值比,1.818;95%置信区间,1.167 - 2.832;P = 0.008)。此外,Kaplan-Meier分析表明,TNFAIP8高表达的IDC患者的生存时间短于TNFAIP8低表达的患者,多因素分析表明,TNFAIP8是IDC患者总生存和无病生存的独立预后因素(分别为P = 0.041和P = 0.020)。因此,TNFAIP8过表达可能促进肿瘤进展,它可能是IDC患者的一种新型预后生物标志物。

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