Clinical prognostication and immunotherapy response prediction in esophageal squamous cell carcinoma using the DNA damage repair‐associated signature

Abstract

AbstractBackgroundThe relationship between DNA damage repair (DDR) and cancer is intricately intertwined; however, its specific role in esophageal squamous cell carcinoma (ESCC) remains enigmatic.MethodsEmploying 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.ResultsNotably, 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.ConclusionThrough 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.