A damage-associated molecular patterns-related gene signature for the prediction of prognosis and immune microenvironment in children stage III acute lymphoblastic leukemia.

Background: Immunogenic cell death (ICD)-mediated immune response provides a strong rationale to overcome immune evasion in acute lymphoblastic leukemia (ALL). ICD will produce damage-associated molecular patterns (DAMPs) in tumor microenvironment. However, there are few studies on the application of DAMPs-related molecular subtypes in clinically predicting stage III of ALL prognosis. The current study is to identify the DAMPs-associated genes and their molecular subtypes in the stage III of ALL and construct a reliable risk model for prognosis as well as exploring the potential immune-related mechanism.

Materials And Methods: We used Target and EBI database for differentially expressed genes (DEGs) analysis of the stage III pediatric ALL samples. Three clusters were identified based on a consistent clustering analysis. By using Cox regression and LASSO analysis, we determined DEGs that attribute to survival benefit. In addition, the Gene Set Enrichment Analysis (GSEA) was performed to identify potential molecular pathways regulated by the DAMPs-related gene signatures. ESTIMATE was employed for evaluating the composition of immune cell populations.

Results: A sum of 146 DAMPs-associated DEGs in ALL were determined and seven transcripts among them were selected to establish a risk model. The DAMPs-associated gene signature significantly contributed to worse prognosis in the high-risk group. We also found that the high-risk group exhibited low immune cell infiltration and high expression of immune checkpoints.

Conclusion: In summary, our study showed that the DAMPs-related DEGs in the stage III of children ALL could be used to predict their prognosis. The risk model of DAMPs we established may be more sensitive to immunotherapy prediction.