Investigating the impact of STING pathway activation on breast cancer treatment outcomes: development and validation of a prognostic model

作者：Yangyan Zhong, Hong Cao, Wei Li, Jian Deng, Dan Li, Junjie Deng · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1438364 · 被引用次数：6 · 研究领域：interferon and immune responses、Ferroptosis and cancer prognosis、Cancer Immunotherapy and Biomarkers

Introduction: Breast cancer (BRCA) is a significant cause of cancer-associated mortality across the globe. Current therapeutic approaches face challenges such as drug resistance and metastasis. Immune signaling is triggered by chromosomal instability (CIN) generates misplaced DNA structures that activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, triggering. Studies have linked STING activation to BRCA treatment. Methods: The bulk RNA-seq data for patients with BRCA were collected from the TCGA-BRCA cohort, GSE20685, and GSE96058 cohorts. STING pathway-related genes (SRGs) were obtained from the Reactome database. Differentially expressed genes were analyzed using the limma package. Immune cell infiltration was analyzed using the IOBR package. Gene Ontology biological processes, Kyoto Encyclopedia of Genes and Genomes pathways, and cancer hallmark pathways were analyzed using the MSigDB database. Prognostic models were prepared using the least absolute shrinkage and selection operator and multiple-factor Cox regression analysis. Single-cell analysis was performed using the Seurat and SCP pipeline. Results: The expression patterns and clinical relevance of SRGs were analyzed in patients with BRCA. Transcriptional differences in the SRGs were observed between normal and tumorous tissues, with global down-regulated STING1 and up-regulated TBK1 in BRCA tissue. Tumor tissues were classified through consensus clustering analysis into two distin...