High expression of tumor necrosis factor receptor-associated factor 2 promotes tumor metastasis and is associated with unfavorable prognosis in gastric cancer
High expression of tumor necrosis factor receptor-associated factor 2 promotes tumor metastasis and is associated with unfavorable prognosis in gastric cancer
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肿瘤坏死因子受体相关因子2的高表达促进肿瘤转移并与胃癌不良预后相关
DOI：
10.1111/jgh.13818
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发表时间：
2018
影响因子：
4.1
通讯作者：
Qin Xinyu
中科院分区：
文献类型：
--
作者：
Zhao Junjie;Li Haojie;Min Lingqiang;Han Xu;Shu Ping;Yang Yupeng;Gan Qiangjun;Wang Xuefei;Wang Hongshan;Ruan Yuanyuan;Qin Jing;Sun Yihong;Qin Xinyu
肿瘤坏死因子受体相关因子2（TRAF 2）是核因子κ B（NF-κB）活化的关键效应因子。方法采用免疫组化方法检测TRAF 2在胃癌组织中的表达，分析其与胃癌临床病理特征的关系，并应用诺模图预测患者的生存期。此外，我们还通过transwell法检测TRAF 2在促进肿瘤转移中的作用，并探讨TRAF 2与NF-κB和白细胞介素-8（IL-8）之间的相关性。此外，我们研究了TRAF 2和肿瘤微环境之间的相关性，通过免疫组化staining.ResultsIn我们的研究中，我们发现，TRAF 2的表达显着增加在胃癌组织。TRAF 2在胃癌细胞中的高表达与肿瘤的侵袭和转移有关，也是胃癌患者的一个独立的不良预后因素，体外研究发现TRAF 2可增强胃癌细胞NF-κB的活化，进而促进IL-8的表达。抑制NF-κB或IL-8信号传导可减弱TRAF 2诱导的迁移和侵袭能力。高TRAF 2表达被证实与高肿瘤内和血清IL-8水平相关。此外，TRAF 2表达与中性粒细胞和巨噬细胞浸润以及微血管形成在胃癌samples.ConclusionsThese结果表明，TRAF 2功能作为一个重要的调制器在肿瘤转移和肿瘤微环境的形成，是一个新的独立的胃癌预后因素。
BackgroundTumor necrosis factor receptor‐associated factor 2 (TRAF2) is a key effector in the activation of nuclear factor kappa B (NF‐κB). Nevertheless, the role of TRAF2 in gastric tumorigenesis remains little defined.MethodsImmunohistochemistry was used to find the relationship between TRAF2 expression and clinicopathological characteristics of gastric cancer patients, and nomogram was applied to predict the overall survival of patients. Besides, we performed transwell assays to detect the function of TRAF2 in promoting metastasis and explored the correlations between TRAF2, NF‐κB, and interleukin‐8 (IL‐8)in vitro. In addition, we examined the correlation between TRAF2 and tumor microenvironment by immunohistochemistry staining.ResultsIn our study, we found that TRAF2 expression was markedly increased in gastric cancer tissues. High intratumoral TRAF2 staining, which was associated with tumor invasion and metastasis, was also an independent poor prognosticator for gastric cancer patients.In vitrostudies revealed that TRAF2 enhanced NF‐κB activation and subsequent IL‐8 expression in gastric cancer cells. Inhibition of NF‐κB or IL‐8 signaling attenuated TRAF2‐induced migration and invasion abilities. High TRAF2 expression was confirmed to be associated with both high intratumoral and serum levels of IL‐8. In addition, TRAF2 expression was positively correlated with neutrophil and macrophage infiltration as well as microvessels formation in gastric cancer samples.ConclusionsThese results suggest that TRAF2 functions as an important modulator in tumor metastasis and tumor microenvironment formation and is a novel independent prognostic factor of gastric cancer.