High cGAS-STING expression associates with improved efficacy of neoadjuvant chemo-immunotherapy in head and neck squamous cell carcinoma.

IF 3.5 3区医学 Q2 ONCOLOGY

Frontiers in Oncology Pub Date : 2025-07-15 eCollection Date: 2025-01-01 DOI:10.3389/fonc.2025.1584061

Miao Wang, Menglin Shi, Yiming Ding, Zishanbai Zhang, Yuze Ge, Zhixin Li, Yixin Jing, Honglian Hu, Xiaohong Chen

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引用次数: 0

Abstract

Purpose: Neoadjuvant chemo-immunotherapy (NACI) has demonstrated significant clinical advantages in head and neck squamous cell carcinomas (HNSCC), while clinical responses vary in different patients. This study investigated the correlation between the cyclic GMP-AMP synthase (cGAS, CGAS) and the stimulator of interferon genes (STING, STING1) expressions and the efficacy of NACI in HNSCC.

Methods: The correlation between CGAS and STING1 expressions and chemotherapy/immunotherapy drug sensitivity was analyzed using the GDSC and TCIA dataset. The study enrolled 38 HNSCC patients receiving NACI, with protein expressions of cGAS and STING evaluated via immunohistochemistry. The T cell abundance and tumor-T cell interactions in different CGAS and STING1 expression groups were analyzed using bulk RNA-seq and scRNA-seq data from open databases.

Results: The mRNA expressions of CGAS and STING1 were negatively correlated with the IC50 of docetaxel and positively correlated with the efficacy of anti-PD-1 treatment (p<0.05). In the real-world cohort, cGAS and STING expressions were both positively related to NACI efficacy (p<0.05). The mRNA expressions of CGAS and STING1 were positively correlated with the abundance of Act-CD4 (CGAS: rho=0.416, p<2.21e-16; STING1: rho=0.26, p=1.82e-09), Act-CD8 (CGAS: rho=0.089, p=0.0425; STING1: rho=0.303, p=1.98e-12), NKT cell (CGAS: rho=0.255, p=0.3.78e-09; STING1: rho=0.375, p=2.2e-6). Tumor cells with increased expression of CGAS or STING1 showed enhanced interactions with T cells.

Conclusion: This study confirms the positive correlation between cGAS and STING expressions and NACI efficacy, suggesting their role in immune activation and potential as biomarkers for predicting NACI efficacy in HNSCC.

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cGAS-STING高表达与头颈部鳞状细胞癌新辅助化疗免疫治疗的疗效提高有关。

目的：新辅助化疗免疫治疗（NACI）在头颈部鳞状细胞癌（HNSCC）中显示出显著的临床优势，但不同患者的临床反应不同。本研究探讨环GMP-AMP合成酶（cGAS, cGAS）与干扰素刺激基因（STING, STING1）表达与NACI治疗HNSCC疗效的相关性。方法：采用GDSC和TCIA数据集分析CGAS和STING1表达与化疗/免疫治疗药物敏感性的相关性。该研究招募了38例接受NACI治疗的HNSCC患者，通过免疫组织化学评估cGAS和STING的蛋白表达。使用开放数据库的大量RNA-seq和scRNA-seq数据分析不同CGAS和STING1表达组的T细胞丰度和肿瘤-T细胞相互作用。结果：CGAS、STING1 mRNA表达量与多西他赛IC50呈负相关，与抗pd -1治疗效果呈正相关(pCGAS、STING1与Act-CD4丰度呈正相关（CGAS: rho=0.416, pSTING1: rho=0.26, p= 1.822 -09）、Act-CD8 (CGAS: rho=0.089, p=0.0425；STING1: rho=0.303, p=1.98e-12)， NKT细胞(CGAS: rho=0.255, p=0.3.78e-09；STING1: rho=0.375, p= 2.22 -6)。CGAS或STING1表达增加的肿瘤细胞与T细胞的相互作用增强。结论：本研究证实了cGAS和STING表达与NACI疗效呈正相关，提示其在HNSCC中具有免疫激活作用和作为预测NACI疗效的生物标志物的潜力。

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

Frontiers in Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

6.20

自引率

10.60%

发文量

6641

审稿时长

14 weeks

期刊介绍： Cancer Imaging and Diagnosis is dedicated to the publication of results from clinical and research studies applied to cancer diagnosis and treatment. The section aims to publish studies from the entire field of cancer imaging: results from routine use of clinical imaging in both radiology and nuclear medicine, results from clinical trials, experimental molecular imaging in humans and small animals, research on new contrast agents in CT, MRI, ultrasound, publication of new technical applications and processing algorithms to improve the standardization of quantitative imaging and image guided interventions for the diagnosis and treatment of cancer.