Decreased expression of STING predicts poor prognosis in patients with gastric cancer.
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.
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
Shushu
S
Song
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
Peike
P
Peng
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
Zhaoqing
Z
Tang
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
Junjie
J
Zhao
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
Weicheng
W
Wu
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
Haojie
H
Li
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
Miaomiao
M
Shao
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
Lili
L
Li
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
Caiting
C
Yang
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China.
Fangfang
F
Duan
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
Mingming
M
Zhang
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China.
Jie
J
Zhang
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
Hao
H
Wu
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
Can
C
Li
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
Xuefei
X
Wang
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
Hongshan
H
Wang
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.
Yuanyuan
Y
Ruan
Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China.
Jianxin
J
Gu
D014408:Biomarkers, Tumor / Q000378:metabolism; D001733:Bites and Stings / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D057089:Pathology, Molecular; D011237:Predictive Value of Tests; D011379:Prognosis; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D016019:Survival Analysis; D047368:Tumor Burden
D014408:Biomarkers, Tumor