An Analysis of the Expression and Association with Immune Cell Infiltration of the cGAS/STING Pathway in Pan-Cancer - PubMed (original) (raw)

doi: 10.1016/j.omtn.2018.11.003. Epub 2018 Nov 20.

Yuanyuan Zhu 1, Tongsen Zheng 2, Guangyu Wang 2, Minghui Zhang 3, Jiade Li 4, Hongbo Ji 3, Shijun Li 5, Shucai Yang 6, Dandan Xu 7, Zhiwei Li 2, Tianzhen Wang 1, Yan He 1, Lei Zhang 1, Weiwei Yang 1, Ran Zhao 1, Dapeng Hao 8, Xiaobo Li 9

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

Xiang An et al. Mol Ther Nucleic Acids. 2019.

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.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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Graphical abstract

Figure 1

Figure 1

The Expression of the cGAS/STING Pathway in Different Types of Cancer TCGA RNA-seq data were first TPM normalized, and the differential expression was assessed by an unpaired t test to generate a p value. (A) The expression of MB21D1 in pan-cancer. (B) The expression of TMEM173 in pan-cancer. (C) The expression of TBK1 in pan-cancer. (D) The expression of IRF3 in pan-cancer. *p < 0.05; **p < 0.01; ***p < 0.001.

Figure 2

Figure 2

Promoter Methylation Level of the cGAS/STING Pathway in Different Types of Cancer The p value was assessed by an unpaired t test. (A) Methylation level of MB21D1 gene promoter. (B) Methylation level of TMEM173 gene promoter. (C) Methylation level of TBK1 gene promoter. (D) Methylation level of IRF3 gene promoter. *p < 0.05; **p < 0.01; ***p < 0.001.

Figure 3

Figure 3

Somatic Mutation Rate of the MB21D1, TMEM173, TBK1, and IRF3 Genes in Various Tumors

Figure 4

Figure 4

The Correlation between the Expression of cGAS/STING Signaling and the Infiltration of Immune Cells (A) The correlation between the expression of MB21D1, TMEM173, TBK1, IRF3, and the infiltration of activated CD4, CD8 T cell, and DC. Node color is determined by correlation, and node size indicates the significance of correlation. (B) The high expression of TMEM173 predicts a favorable prognosis of metastatic melanoma patients treated with monoclonal antibody against CTLA-4. (C) The high expression of TBK1 indicates a favorable prognosis of metastatic melanoma patients treated with monoclonal antibody against CTLA-4.

Figure 5

Figure 5

cGAS/STING Pathway Expression as a Prognostic Factor in Various Tumors (A) MB21D1. (B) TBK1. (C) IRF3.

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