Decoding the cGAS-STING-eosinophils predictive and natural therapeutic molecular signature in burn injury progression and keloid formation: insights from artificial intelligence-driven multiomics
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1Department of Comprehensive Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
Inflammation-related pathway activation contributes to the progression of burn injury and keloid formation.
Objective:
Our study aimed to investigate the role of the cGAS-STING pathway in regulating eosinophils during the progression of burn injury and keloid formation.
Methods:
Key cGAS-STING pathway and eosinophils (CE)-related differentially expressed genes (DEGs) were identified in burn injury patient bulk profiles (GSE19743) using Limma, WGCNA, CIBERSORT, and STRING frameworks. Next, a systemic and explainable machine learning model was utilized to identify predictive model hub genes involved in keloid formation of burn injury patients (GSE37069) and burn-injury-associated keloid patient (GSE42270), based on CE-associated DEGs. The pathogenic role of hub genes and eosinophils in keloid formation was further assessed in a keloid patient single-cell profile (GSE243716) using cutting-edge single-cell analytical frameworks, such as AUCELL, sctenifoldknk, and Bayesprism. In addition, a deep learning algorithm (DrugRefLector) and molecular docking were employed to identify natural compounds targeting the hub gene for the treatment of burn-injury-associated keloid (GSE42270). Finally, in vitro assays were conducted to validate expression patterns of the hub gene.
Results:
An integrated CE-associated gene signature can indicate keloid formation in burn injury patients. CCL5 can be considered as an up-regulated pathogenic factor and therapeutic target for Icariin, which is involved in keloid pathogenesis.
Conclusion:
This is the first study to identify a CA-associated signature in keloid formation among burn injury patients.
