Decreased expression of STING predicts poor prognosis in patients with gastric cancer.
Decreased expression of STING predicts poor prognosis in patients with gastric cancer.
复制标题
STING表达降低预示胃癌患者预后不良
DOI：
10.1038/srep39858
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发表时间：
2017-02-08
影响因子：
4.6
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Song S;Peng P;Tang Z;Zhao J;Wu W;Li H;Shao M;Li L;Yang C;Duan F;Zhang M;Zhang J;Wu H;Li C;Wang X;Wang H;Ruan Y;Gu J
STING（stimulator of interferon genes，干扰素基因的刺激因子）通过调节I型干扰素信号传导和先天免疫在宿主防御病毒和细胞内细菌中发挥重要作用。幽门螺杆菌的慢性感染被认为是胃癌最强的危险因素。因此，我们的目的是探讨STING信号在胃癌发生发展中的作用。采用免疫组化法检测217例胃癌手术切除标本中STING的表达。STING蛋白在肿瘤组织中的表达明显低于非肿瘤组织，且STING蛋白表达强度与肿瘤大小、浸润深度、淋巴结转移、TNM分期及患者生存期相关。多因素分析显示STING是一个独立的预后因子，将其纳入TNM分期系统可以提高总生存期的预测准确性;体外研究显示STING的敲低可以促进胃癌细胞的集落形成、存活、迁移和侵袭，并导致胞浆DNA传感缺陷。另外，慢性病。pylori感染上调小鼠STING表达并激活STING信号传导。STING是一个新的独立的胃癌预后因子和潜在的免疫靶点。
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 withHelicobacter pyloriis 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 vitrostudies 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, chronicH. pyloriinfection 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.