An Analysis of the Expression and Association with Immune Cell Infiltration of the cGAS/STING Pathway in Pan-Cancer

Xiang An; Yuanyuan Zhu; Tongsen Zheng; Guangyu Wang; Minghui Zhang; Jiade Li; Hongbo Ji; Shijun Li; Shucai Yang; Dandan Xu; Zhiwei Li; Tianzhen Wang; Yan He; Lei Zhang; Weiwei Yang; Ran Zhao; Dapeng Hao; Xiaobo Li

doi:10.1016/j.omtn.2018.11.003

An Analysis of the Expression and Association with Immune Cell Infiltration of the cGAS/STING Pathway in Pan-Cancer

Mol Ther Nucleic Acids. 2019 Mar 1:14:80-89. doi: 10.1016/j.omtn.2018.11.003. Epub 2018 Nov 20.

Authors

Xiang An¹, Yuanyuan Zhu¹, Tongsen Zheng², Guangyu Wang², Minghui Zhang³, Jiade Li⁴, Hongbo Ji³, Shijun Li⁵, Shucai Yang⁶, Dandan Xu⁷, Zhiwei Li², Tianzhen Wang¹, Yan He¹, Lei Zhang¹, Weiwei Yang¹, Ran Zhao¹, Dapeng Hao⁸, Xiaobo Li⁹

Affiliations

¹ Department of Pathology, Harbin Medical University, Harbin 150081, China.
² Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China.
³ Department of Oncology, Chifeng City Hospital, Chifeng 024000, China.
⁴ Department of Cancer Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin 150081, China.
⁵ Department of Pathology, Chifeng City Hospital, Chifeng 024000, China.
⁶ Department of Anatomy, Harbin Medical University, Harbin 150081, China.
⁷ Department of Biology, Faculty of Science, Harbin University, Harbin 150000, China.
⁸ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: dapeng.hao@gmail.com.
⁹ Department of Pathology, Harbin Medical University, Harbin 150081, China; North China Translational Medicine Research and Cooperation Center (NTMRC), Harbin 150081, China. Electronic address: lixiaobo@ems.hrbmu.edu.cn.

Abstract

Recent evidence shows that cyclic GMP-AMP synthase (cGAS)/stimulator of interferon (IFN) genes (STING) signaling is essential for antitumor immunity by inducing the production of type I IFN and thus activating both innate and adaptive immunity based on gene knockout mouse models. However, the extensive detection of the expression of cGAS/STING signaling in human cancer and mining the roles of this signaling pathway in human cancer immunity have not been performed until now. In this study, we revealed that four key molecules (cGAS, STING, TANK binding kinase 1 [TBK1], and IFN regulatory factor 3 [IRF3]) in the cGAS/STING signaling are highly expressed in cancer tissues, and the expression levels of these genes are negatively correlated with their methylation levels in most of the detected cancer types. We also showed that highly upregulated cGAS/STING signaling is negatively correlated with the infiltration of immune cells in some tumor types, and consistent with these findings, we showed that a high level of cGAS/STING signaling predicts a poor prognosis in patients with certain cancers. This study suggests that it is necessary to deeply and fully evaluate the function of cGAS/STING signaling in cancer immunity and cancer progression before the application of the STING agonist-based anticancer immune therapy in the clinic.

Keywords: cGAS/STING; immune infiltration; interferon; methylation; prognosis.