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

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. 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.