Analysis Of The Influence Of Pyroptosis Genes On The Prognosis Of Acute Myeloid Leukemia And Tumor Immune Microenvironment Based On Bioinformatics

Objective:Acute myeloid leukemia（AML）is a common and fatal hematological malignancy in adults with an extremely low 5-year survival rate.As a novel inflammatory form of programmed cell death,pyroptosis is a prospective target for cancer therapy.Nevertheless,little is known about the association between pyroptosis-related genes（PRGs）and AML prognosis.Herein,we systematically investigated the specific functions and clinical prognostic value of multiple PRGs in AML.Methods:The expression,somatic mutation and copy number variation of 42 PRGs were evaluated in AML based on TCGA and GTEx dataset.Their interactions and prognostic value were subsequently observed.A PRG signature was generated via univariate Cox and LASSO Cox regression analysis.The predictive efficacy of survival was examined using survival analysis,ROC,univariate and multivariate Cox analysis,and subgroup analysis and validated in the Beat AML cohort.In addition,we investigated the specific biological functions of the high-and low-risk groups and analyzed the association between risk score and immune cell infiltration,HLA,immune checkpoints,cancer stem cell（CSC）,tumor mutation burden（TMB）,and therapeutic drug sensitivity.Results:In this study,we found that a strong interaction between CNV and gene transcriptomic expression levels could be observed among PRGs with abnormal expression in AML.The majority of PRGs were expressed aberrantly in AML.The CEBPB,PLCG1,and VDR were significantly low in expression accompanied by CNV deletion,and TIRAP was significantly high in expression accompanied by CNV amplification.The closely interaction could be observed between them.Subsequently,a 6-PRGs signature was generated,including CASP3,ELANE,GSDMA,NOD1,PYCARD and VDR.High risk score represented poorer prognosis and it was validated that PRG risk score was independent and sensitive predictor of prognosis.Meanwhile,a nomogram including cytogenetic risk,age and risk score was constructed for accurate prediction of 1-,3-and 5-year survival probabilities.Additionally,this PRG risk score was significantly associated with the tumor immune microenvironment（TIME）.High PRG risk score with high immune cell infiltration,HLA and immune checkpoints.This risk score was significantly and negatively associated with CSC and TMB.We observed that patients with low PRG risk score presented significantly lower IC₅₀ value for ATRA,cytarabine,midostaurin,doxorubicin,and etoposide.Conclusion:Our findings might contribute to further understanding of PRGs in the prognosis and development of AML and provide novel and reliable biomarkers for its precise prevention and treatment.