A Gene Signature Comprising Seven Pyroptosis-Related Genes Predicts Prognosis in Pediatric Patients with Acute Myeloid Leukemia

Abstract

<b><i>Introduction:</i></b> The aim of the study was to construct a pyroptosis-related risk score (RS) model for the prognosis of acute myeloid leukemia (AML). <b><i>Methods:</i></b> The TARGET (training) and E-MTAB-1216 (validation) datasets were downloaded. Pyroptosis-related genes with differences in expression were identified between the recurrent and nonrecurrent samples of the training dataset. An RS prognostic model comprising seven pyroptosis-related genes was constructed using LASSO regression coefficients. The samples were classified into the high- and low-risk groups using the RS model; the differentially expressed genes (DEGs) between these groups were identified, followed by DEG functional analysis and the immunological evaluation of these groups. <b><i>Results:</i></b> Forty-nine pyroptosis-related genes, including 22 DEGs, were screened. <i>WT1</i>, <i>NPM</i>, <i>FLT3/ITD</i>, and <i>CEBPA</i> mutations were found in most pediatric AML samples. An RS prognostic model was constructed using 7 pyroptosis-related genes. The two risk groups and prognostic data were significantly related. <i>FLT3/ITD</i> mutations, <i>CEBPA</i> mutations, and RS model status were identified as independent prognostic factors, using the clinical information. The DEGs between the two groups were correlated with immune-related pathways. Moreover, the immune cell distribution and the occurrence of immune-related pathways were notably decreased in the high-risk group. <b><i>Discussion/Conclusion:</i></b> Seven pyroptosis-related genes, <i>CHMP2A</i>, <i>PRKACA</i>, <i>CASP9</i>, <i>IRF2</i>, <i>CHMP3</i>, <i>HMGB1</i>, and <i>AIM2</i>, can predict the prognosis and recurrence of childhood AML.