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

Abstract

Introduction: To construct a pyroptosis-related risk score (RS) model for the prognosis of acute myeloid leukemia (AML). Methods: The TARGET (training) and E-MTAB-1216 (validation) datasets were downloaded. Pyroptosis-related genes with differences in expression were identified between the recurrent and non-recurrent 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. Results: Forty-nine pyroptosis-related genes, including 22 DEGs, were screened. WT1, NPM, FLT3/ITD, and CEBPA mutations were found in most pediatric AML samples. An RS prognostic model was constructed using seven pyroptosis-related genes. The two risk groups and prognostic data were significantly related. FLT3/ITD mutations, CEBPA 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 occurrence of immune-related pathways were notably decreased in the high-risk group. Discussion/Conclusion: Seven pyroptosis-related genes, CHMP2A, PRKACA, CASP9, IRF2, CHMP3, HMGB1, and AIM2, can predict the prognosis and recurrence of childhood AML.

Development of a novel pyroptosis-related LncRNA signature with multiple significance in acute myeloid leukemia

“…Accumulating evidences indicated that chronic inflammation in tumor microenvironment (TME) played a major role in immune invasion, thus contributing to tumorigenesis (Grivennikov et al, 2010;Shin and Brusselle, 2014; Frontiers in Genetics frontiersin.org Lu et al, 2021). In some studies of pyroptosis in AML, TME was found remarkably different between risk groups (He et al, 2022;Shao et al, 2022;Zhou et al, 2022). Pyroptosis, an inflammationdependent form of PCD, was proved to participate in tumor growth and chemosensitivity (Xia et al, 2019), while its mechanisms are complicated.…”

“…Previous studies suggested the high-risk group of pyroptosis-related signature was enriched in immunosuppressive cells and had lower drug sensitivity to classical chemotherapy ( Pan et al, 2022 ; Shao et al, 2022 ; Zhou et al, 2022 ). In pediatric patients with AML, PRGs were found to predict recurrence ( He et al, 2022 ). To probe the underlying mechanisms further of our signature, the TME and enrichment analysis between risk subgroups were investigated.…”

“…The researches for the relationship between pyroptosis and tumor may provide some inspirations for clinical treatments. Recent several researches showed pyroptosis-related protein-coding genes could predict prognosis in AML ( He et al, 2022 ; Liu et al, 2022 ; Pan et al, 2022 ; Shao et al, 2022 ; Zhou et al, 2022 ).…”

Vacuolar ATPase Is a Possible Therapeutic Target in Acute Myeloid Leukemia: Focus on Patient Heterogeneity and Treatment Toxicity

“…Finally, the mechanisms of regulated AML cell death and their modulation/regulation by V-ATPase need further characterization [4,5]. Several forms of programmed cell death may be operative in human AML [118][119][120][121][122][123][124][125][126][127][128][129][130][131], including endoplasmic reticulum stress-induced apoptosis [69]; possibly autophagy-associated apoptosis, although autophagy is generally regarded as a survival mechanism [120]; ferroptosis due to lethal iron accumulation [5,[118][119][120][121][122][123][124]; inflammatory necroptosis [124][125][126][127] and pyroptosis [128,129]; oncosis [130]; apoptosis-like anoikis due to loss of cell anchorage [5,131]; and pH-dependent alkaliptosis [5]. Thus, programmed cell death in AML cells can have a mixed etiology, including apoptosis (which seems particularly important), together with other forms of programmed cell death.…”