Dissociation between the expression of cGAS/STING and a senescence-associated signature in colon cancer.

IF 3.5 3区医学

International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI:10.1177/03946320251324821

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

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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, 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.

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结肠癌中cGAS/STING表达与衰老相关信号的分离

目的：cGAS/STING通路在体内抗肿瘤免疫中的作用及其与衰老的关系有待进一步研究。细胞衰老及其分泌表型（SASP）可能通过cGAS/STING途径参与肿瘤免疫微环境的调节。方法：收集配对结肠癌及癌旁非恶性黏膜的基因表达数据（98例，n = 196份样本）；65例患者（n = 130份样本）进行了cGAS/STING和衰老特征分析。免疫组化检测124例结直肠标本中cGAS/STING蛋白的表达。结果：大约四分之一的患者在两个基因组中都表现出衰老特征，但与cGAS/STING表达没有显著相关性。值得注意的是，与非恶性结肠黏膜相比，肿瘤组织中cGAS的表达高于STING。蛋白分析显示cGAS阳性表达83%，STING阳性表达39%，表达模式存在差异。此外，15%的样品缺乏这两种标记物，而35%的样品显示两种标记物的阳性染色。cGAS/STING状态与肿瘤分期、患者年龄、淋巴血管浸润或淋巴结受累无显著相关性。结论：我们的研究结果表明，衰老标志物在结直肠癌样本中表达显著，但与cGAS/STING无关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Immunopathology and Pharmacology Immunology and Microbiology-Immunology

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期刊介绍： International Journal of Immunopathology and Pharmacology is an Open Access peer-reviewed journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The intention is that the journal should reflect both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.