Clinical prognostication and immunotherapy response prediction in esophageal squamous cell carcinoma using the DNA damage repair-associated signature.
Environ Toxicol
; 39(5): 2803-2816, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38287713
ABSTRACT
BACKGROUND:
The relationship between DNA damage repair (DDR) and cancer is intricately intertwined; however, its specific role in esophageal squamous cell carcinoma (ESCC) remains enigmatic.METHODS:
Employing single-cell analysis, we delineated the functionality of DDR-related genes within the tumor microenvironment (TME). A diverse array of scoring mechanisms, including AUCell, UCell, singscore, ssgsea, and AddModuleScore, were harnessed to scrutinize the activity of DDR-related genes across different cell types. Differential pathway alterations between high-and low-DDR activity cell clusters were compared. Furthermore, leveraging multiple RNA-seq datasets, we constructed a robust DDR-associated signature (DAS), and through integrative multiomics analysis, we explored differences in prognosis, pathways, mutational landscapes, and immunotherapy predictions among distinct DAS groups.RESULTS:
Notably, high-DDR activity cell subpopulations exhibited markedly enhanced cellular communication. The DAS demonstrated uniformity across multiple datasets. The low-DAS group exhibited improved prognoses, accompanied by heightened immune infiltration and elevated immune checkpoint expression. SubMap analysis of multiple immunotherapy datasets suggested that low-DAS group may experience enhanced immunotherapy responses. The "oncopredict" R package analyzed and screened sensitive drugs for different DAS groups.CONCLUSION:
Through the integration of single-cell and bulk RNA-seq data, we have developed a DAS associated with prognosis and immunotherapy response. This signature holds promise for the future stratification and personalized treatment of ESCC patients in clinical settings.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Esofágicas
/
Carcinoma de Células Escamosas do Esôfago
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article