High TNFAIP6 level is associated with poor prognosis of urothelial carcinomas
High TNFAIP6 level is associated with poor prognosis of urothelial carcinomas
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DOI：
10.1016/j.urolonc.2018.12.009
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发表时间：
2019-04-01
影响因子：
2.7
通讯作者：
Li, Wei-Ming
中科院分区：
文献类型：
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作者：
Chan, Ti-Chun;Li, Chien-Feng;Li, Wei-Ming
目的：炎症反应影响癌发生的每个阶段，从开始，通过入侵，转移。研究表明，由环境和职业暴露引起的慢性炎症会增加患尿路上皮癌（UC）的风险。使用已发表的UC转录组（GSE 32894），我们鉴定了在与炎症反应相关的基因（GO：0006954）中，TNFAIP 6在UC进展期间显著上调。因此，我们研究了TNFAIP 6与疾病特征，转移和生存在我们的特征良好的队列UC.Methods：我们确定TNFAIP 6表达在340上尿路UC（UTUC）和295膀胱UC（UBUC）使用免疫组化和评估结果使用H-评分。TNFAIP 6表达与临床病理特征、疾病特异性生存率和无转移生存率相关。采用Kaplan-Meier曲线和考克斯比例风险模型进行生存分析。结果：TNFAIP 6高表达与肿瘤的病理分期、淋巴结转移、神经周围浸润、血管浸润和核分裂活跃程度密切相关。多变量分析确定TNFAIP 6高表达是疾病特异性生存的独立预测因子（UTUC的风险比：2.891，P = 0.003; UBUC：2.175，P = 0.017）和无转移生存率（UTUC的风险比：3.803，P < 0.001; UBUC：3.845，P < 0.001）。TNFAIP 6高表达与UC的侵袭性临床病理特征和不良预后相关，这表明它可以作为一种新的治疗靶点。TNFAIP 6免疫染色可与当前病理学检查一起使用，以更好地对UC进行风险分层。(C)2018爱思唯尔公司All rights reserved.
Purpose: Inflammatory responses affect each stage of carcinogenesis, from initiation, through invasion, to metastasis. Studies have shown that chronic inflammation induced by environmental and occupational exposures increase the risk of developing urothelial carcinoma (UC). Using a published UC transcriptome (GSE32894), we identified that among genes associated with inflammatory response (GO: 0006954), TNFAIP6 was significantly upregulated during UC progression. Therefore, we investigated the association of TNFAIP6 with disease features, metastasis and survival in our well-characterized cohort of UC.Methods: We determined TNFAIP6 expression in 340 upper urinary tract UCs (UTUC) and 295 urinary bladder UCs (UBUC) using immunohistochemistry and evaluated the results using H-score. TNFAIP6 expression correlated with clinicopathological features, disease-specific survival, and metastasis-free survival. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards model.Results: High TNFAIP6 expression was significantly associated with advanced pathological stage, lymph node metastasis, perineural invasion, vascular invasion, and high mitotic activity. Multivariate analysis identified high TNFAIP6 expression as an independent predictor of disease-specific survival (hazard ratio in UTUC: 2.891, P = 0.003; in UBUC: 2.175, P = 0.017) and metastasis-free survival (hazard ratio in UTUC: 3.803, P < 0.001; in UBUC: 3.845, P < 0.001).Conclusion: High TNFAIP6 expression is associated with aggressive clinicopathological features and poor prognosis in UCs, suggesting it may serve as a novel prognosticator and treatment target. TNFAIP6 immunostaining may be used with current pathological examinations for better risk stratification for UCs. (C) 2018 Elsevier Inc. All rights reserved.