Identification of Cytosolic DNA Sensor cGAS-STING as Immune-Related Risk Factor in Renal Carcinoma following Pan-Cancer Analysis.

Autor: Wu Z; Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China., Lin Y; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China., Liu LM; Department of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China., Hou YL; Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China., Qin WT; Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China., Zhang L; Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China., Jiang SH; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China., Yang Q; Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.; Shanghai Institute of Precision Medicine, Shanghai 200125, China., Bai YR; Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Jazyk: angličtina
Zdroj: Journal of immunology research [J Immunol Res] 2022 Aug 09; Vol. 2022, pp. 7978042. Date of Electronic Publication: 2022 Aug 09 (Print Publication: 2022).
DOI: 10.1155/2022/7978042
Abstrakt: Background: The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) plays critical functions in innate immune responses via the production of the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), which stimulates the adaptor stimulator of interferon genes (STING). However, the clinical relevance and prognostic value of the cGAS-STING pathway in human cancers remains largely unexplored.
Methods: A gene signature related to the cGAS-STING score was identified. The pan-cancer landscape of cGAS-STING expression was calculated using the RNAseq data acquired from the TCGA cohort. Tumor-infiltrating immune cells (TIICs) were determined by the ssGSEA method. Kaplan-Meier curves, Cox regression analyses, and the area under the curve (AUC) were employed to decipher the predictive value of cGAS-STING risk score and TIICs across several human cancers.
Results: Most tumor tissues displayed a higher cGAS-STING score compared with their corresponding nontumor tissues, except for prostate adenocarcinoma (PRAD) and uterine corpus endometrial carcinoma (UCEC). Higher cGAS-STING score was closely associated with poor clinical outcome of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP), whereas the cGAS-STING score predicted a better prognosis in pheochromocytoma and paraganglioma (PCPG). Enrichment analysis showed that cGAS-STING was profoundly implicated in diverse immune-related pathways in KIRC, KIRP, and PCPG. Significant positive correlations were noticed between cGAS-STING score and TIICs, including activated CD8+ T cells, activated CD4+ T cells, monocytes, and mast cells. Finally, the cGAS-STING score was revealed to be an independent prognostic factor for KIRC patients and possessed a strong predictive power for the prognostic evaluation of KIRC and KIRP patients.
Conclusions: We constructed a cGAS-STING gene signature to predict survival and tumor immunity across human cancers, which can serve as a novel prognostic indicator and therapeutic target, especially in KIRC and KIRP.
Competing Interests: The authors declare that they have no competing interests.
(Copyright © 2022 Zheng Wu et al.)
Databáze: MEDLINE
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