Decreased expression of STING predicts poor prognosis in patients with gastric cancer

被引:184
作者
Song, Shushu [1 ,2 ]
Peng, Peike [1 ,2 ]
Tang, Zhaoqing [3 ]
Zhao, Junjie [3 ]
Wu, Weicheng [1 ,2 ]
Li, Haojie [3 ]
Shao, Miaomiao [1 ,2 ]
Li, Lili [1 ,2 ]
Yang, Caiting [1 ,2 ]
Duan, Fangfang [1 ,4 ]
Zhang, Mingming [1 ,2 ]
Zhang, Jie [1 ,4 ]
Wu, Hao [1 ,2 ]
Li, Can [1 ,2 ]
Wang, Xuefei
Wang, Hongshan [3 ]
Ruan, Yuanyuan [1 ,2 ]
Gu, Jianxin [1 ,2 ,4 ]
机构
[1] Fudan Univ, Sch Basic Med Sci, Key Lab Glycoconjugate Res, Minist Publ Hlth, Shanghai, Peoples R China
[2] Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Shanghai, Peoples R China
[3] Fudan Univ, Zhongshan Hosp, Dept Gen Surg, Shanghai, Peoples R China
[4] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China
基金
高等学校博士学科点专项科研基金;
关键词
CYCLIC GMP-AMP; DNA SENSOR; PATHWAY; INFECTION; ACTIVATION; SYNTHASE; IMMUNITY; HBV;
D O I
10.1038/srep39858
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
STING (stimulator of interferon genes) has recently been found to play an important role in host defenses against virus and intracellular bacteria via the regulation of type-I IFN signaling and innate immunity. Chronic infection with Helicobacter pylori is identified as the strongest risk factor for gastric cancer. Thus, we aim to explore the function of STING signaling in the development of gastric cancer. Immunohistochemistry was used to detect STING expression in 217 gastric cancer patients who underwent surgical resection. STING protein expression was remarkably decreased in tumor tissues compared to non-tumor tissues, and low STING staining intensity was positively correlated with tumor size, tumor invasion depth, lymph mode metastasis, TNM stage, and reduced patients' survival. Multivariate analysis identified STING as an independent prognostic factor, which could improve the predictive accuracy for overall survival when incorporated into TNM staging system. In vitro studies revealed that knock-down of STING promoted colony formation, viability, migration and invasion of gastric cancer cells, and also led to a defect in cytosolic DNA sensing. Besides, chronic H. pylori infection up-regulated STING expression and activated STING signaling in mice. In conclusion, STING was proposed as a novel independent prognostic factor and potential immunotherapeutic target for gastric cancer.
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页数:13
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