Identification and validation of prognostic genes associated with m6A-regulated programmed cell death in acute lymphoblastic leukemia

急性淋巴细胞白血病中与m6A调控的程序性细胞死亡相关的预后基因的鉴定和验证

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Abstract

This study investigated the prognostic significance of m6A-related programmed cell death (PCD) genes in acute lymphoblastic leukemia (ALL). Transcriptomic data from the TCGA-ALL and GSE48558 datasets were analyzed to identify m6A-related PCD genes (corgenes), which were then intersected with 3,063 differentially expressed genes (DEGs), resulting in 23 candidate genes. Univariate Cox regression and LASSO regression analyses identified CFLAR and CDK4 as key prognostic genes, facilitating the construction of a high-accuracy risk prediction model. Gene set enrichment analysis (GSEA) revealed significant pathway differences between the high-risk group (HRG) and the low-risk group (LRG), including olfactory transduction, circadian rhythm, and protein export (adj.P < 0.05). Sensitivity analysis of 60 chemotherapy agents indicated that Bicalutamide was more effective in LRG, while ATRA, CCT018159, PHA-665752, and PLX4720 demonstrated greater efficacy in HRG. RT-qPCR validation confirmed upregulation of CDK4 and downregulation of CFLAR in ALL samples (P < 0.05). This study offers important theoretical support for the prognostic evaluation and personalized treatment strategies in ALL.

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