Research Paper Volume 16, Issue 2 pp 1516—1535
Molecular map of cGAS-STING pathway-related genes in bladder cancer: the perspective toward immune microenvironment and prognosis
- 1 Department of Urology, Hebei General Hospital, Shijiazhuang 050000, China
- 2 Department of Neurology, Xingtai Third Hospital, Xingtai 054000, China
- 3 Department of Thoracic Surgery, Hebei Chest Hospital, Shijiazhuang 050000, China
- 4 Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
- 5 Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
Received: July 6, 2023 Accepted: December 6, 2023 Published: January 17, 2024
https://doi.org/10.18632/aging.205442How to Cite
Copyright: © 2024 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: The cGAS-STING pathway emerges as a pivotal innate immune pathway with the potential to profoundly influence all facets of tumor initiation and progression. The prognostic significance and immunological role of cGAS-STING pathway-related genes (CRGs) in individuals diagnosed with bladder cancer (BLCA) have not yet been fully elucidated.
Methods: Performed unsupervised cluster analysis to identify distinct clusters. Utilizing LASSO and multivariate Cox regression analysis to construct a prognostic risk model. The IMvigor210, GSE13507 and GSE78220 cohorts were utilized to explore the potential value of risk score in immune therapy response and survival prediction.
Results: A risk model was developed utilizing four CRGs in order to forecast the overall survival (OS) of BLCA patients. The risk score to be a standalone risk factor, which was further corroborated by the external validation set obtained from the GEO database (GSE13507). We established an integrated nomogram that combined risk scoring and clinical information, exhibiting commendable clinical practicality in predicting the overall survival period of BLCA patients. It is noteworthy that risk score could differentiate tumor microenvironments among different risk groups and individuals who were more responsive to immunotherapy in IMvigor210 and GSE13507 cohorts. In vitro experiments, we noted an up-regulation of IRF3 and IKBKB upon the activation of the cGAS-STING pathway. Conversely, the activation of the cGAS-STING pathway resulted in a down-regulation of POLR3G and CTNNB1.
Conclusions: CRG risk model shows promise as a potential stratification approach for bladder cancer patients.
Abbreviations
BLCA: bladder cancer; TNM: tumor node metastasis; cGAS-STING: the cyclic GMP-AMP synthase-stimulator of interferon genes; CRGs: the cGAS-STING pathway-related genes; GEO: Gene Expression Omnibus; TCGA: The Cancer Genome Atlas; GTEx: Genotype-Tissue Expression; HPA: Human Protein Atlas; CDF: cumulative distribution function; LASSO: least absolute shrinkage and selection operator; ROC: receiver operating characteristic; DEG: differentially expressed gene; GO: gene ontology; GSVA: gene set variation analysis; GSEA: gene set enrichment analysis; ssGSEA: single-sample gene set enrichment analysis; ICB: immune checkpoint blockade; TCIA: The Cancer Immunome Atlas; RT-qPCR: reverse transcription-quantitative polymerase chain reaction; TIME: tumor immune microenvironment.