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High expression of tumor necrosis factor receptor‐associated factor 2 promotes tumor metastasis and is associated with unfavorable prognosis in gastric cancer
Author(s) -
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
Publication year - 2018
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13818
Subject(s) - metastasis , medicine , cancer research , cancer , immunohistochemistry , tumor necrosis factor alpha , tumor microenvironment , cancer cell , carcinogenesis , pathology
Background Tumor 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. Methods Immunohistochemistry 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. Results In 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 vitro studies 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. Conclusions These 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.