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Updated: May 23, 2025
SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Dissociation between the expression of cGAS/STING and a senescence-associated signature in colon cancer
Sofian Al Shboul1, Ola Abu Al Karsaneh2, Moath Alrjoub3
1Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa, Jordan.
Objective:
The effect of the cGAS/STING pathway on antitumor immunity and its connection to senescence in vivo necessitates further investigation.
Introduction:
Cellular senescence and its secretory phenotype (the SASP) are implicated in modulating the immune microenvironment of cancer possibly through the cGAS/STING pathway.
Methods:
Gene expression data from paired colon cancer and adjacent non-malignant mucosa (98 patients, n = 196 samples; 65 patients, n = 130 samples) were analyzed for cGAS/STING and a senescence signature. Immunohistochemistry assessed cGAS/STING protein expression in 124 colorectal samples.
Results:
Approximately one-quarter of patients displayed senescence profiles in both gene sets, yet without significantly correlating with cGAS/STING expression. Notably, cGAS expression was higher than STING in tumor tissue compared to non-malignant colonic mucosa. Protein analysis showed 83% positive cGAS expression and 39% positive STING expression, with discrepancies in expression patterns. Additionally, 15% of samples lacked both markers, while 35% exhibited positive staining for both. No significant correlations were found between cGAS/STING status and tumor stage, patient age, lymphovascular invasion, or lymph node involvement.
Conclusions:
Our findings demonstrate significant senescence marker expression in colorectal cancer samples but with no correlation with cGAS/STING.
Insights
Colorectal cancer samples show significant senescence markers, but this does not correlate with the cGAS/STING pathway. Further research is needed to understand this complex relationship in antitumor immunity.
Area of Science:
- Immunology
- Oncology
- Cellular Biology
Background:
- Cellular senescence and its secretory phenotype (SASP) influence the tumor immune microenvironment.
- The cGAS/STING pathway is a potential mediator of these immune modulations in cancer.
Purpose of the Study:
- To investigate the relationship between the cGAS/STING pathway and senescence in colorectal cancer.
- To explore the effect of the cGAS/STING pathway on antitumor immunity in vivo.
Main Methods:
- Gene expression analysis of cGAS/STING and senescence signatures in 196 colorectal cancer and adjacent mucosa samples.
- Immunohistochemistry to assess cGAS/STING protein expression in 124 colorectal samples.
Main Results:
- Senescence profiles were observed in approximately 25% of patients but did not correlate with cGAS/STING expression.
- cGAS expression was higher in tumor tissue than non-malignant mucosa; protein analysis revealed varied cGAS/STING expression patterns.
- No significant correlations were found between cGAS/STING status and clinicopathological factors like tumor stage or lymph node involvement.
Conclusions:
- Colorectal cancer samples exhibit significant senescence marker expression.
- There is no observed correlation between senescence markers and the cGAS/STING pathway in this cohort.
- The precise role of cGAS/STING in senescence-associated antitumor immunity in colorectal cancer requires further elucidation.
