高 TNFAIP6 水平与尿路上皮癌的预后不良相关。

High TNFAIP6 level is associated with poor prognosis of urothelial carcinomas.

机构信息

Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan.

Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan; Natioanl Institute of Cancer Research, National Health Research Institute, Tainan, Taiwan; Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.

出版信息

Urol Oncol. 2019 Apr;37(4):293.e11-293.e24. doi: 10.1016/j.urolonc.2018.12.009. Epub 2018 Dec 27.

DOI:10.1016/j.urolonc.2018.12.009

PMID:30595463

Abstract

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.

摘要

目的

炎症反应影响致癌作用的各个阶段，从启动、浸润到转移。研究表明，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。利用已发表的 UC 转录组（GSE32894），我们发现与炎症反应相关的基因（GO：0006954）中，TNFAIP6 在 UC 进展过程中显著上调。因此，我们在经过充分特征描述的 UC 队列中研究了 TNFAIP6 与疾病特征、转移和生存的关联。

方法

我们使用免疫组织化学法测定了 340 例上尿路 UC（UTUC）和 295 例尿膀胱 UC（UBUC）中的 TNFAIP6 表达，并使用 H 评分评估结果。TNFAIP6 表达与临床病理特征、疾病特异性生存和无转移生存相关。生存分析采用 Kaplan-Meier 曲线和 Cox 比例风险模型进行。

结果

高 TNFAIP6 表达与晚期病理分期、淋巴结转移、神经周围侵犯、血管侵犯和高有丝分裂活性显著相关。多变量分析确定高 TNFAIP6 表达是疾病特异性生存（UTUC 的风险比：2.891，P=0.003；UBUC：2.175，P=0.017）和无转移生存（UTUC 的风险比：3.803，P<0.001；UBUC：3.845，P<0.001）的独立预测因子。