Dissociation Between the Expression of CGAS/STING and a Senescence-associated Signature in Colon Cancer

Overview

Journal Int J Immunopathol Pharmacol

Publisher Sage Publications

Specialties Allergy & Immunology
Pathology
Pharmacology

Date 2025 Mar 12

PMID 40070172

Authors

Sofian Al Shboul

Ola Abu Al Karsaneh

Moath Alrjoub

Mohammad Al-Qudah

Mohammed El-Sadoni

Ahmad Alhesa

Mohannad Ramadan

Marwa Barukba

Esraa Fares Al-Quran

Amr Masaadeh

Farah N Almasri

Uruk Shahin

Moureq R Alotaibi

Mohammad Al-Azab

Ashraf I Khasawneh

Tareq Saleh

Affiliations

Soon will be listed here.

Abstract

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, = 196 samples; 65 patients, = 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.

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