Integrative analysis of epigenetic subtypes in acute myeloid Leukemia: A multi-center study combining machine learning for prognostic and therapeutic insights

Jincan Li and Shengyue Wang

PLOS ONE, 2025, vol. 20, issue 5, 1-26

Abstract: Background: Acute Myeloid Leukemia (AML) exhibits significant heterogeneity in clinical outcomes, yet current prognostic stratification systems based on genetic alterations alone cannot fully capture this complexity. This study aimed to develop an integrated epigenetic-based classification system and evaluate its prognostic value. Methods: We performed multi-omics analysis on five independent cohorts totaling 1,103 AML patients. The Cancer Genome Atlas-Acute Myeloid Leukemia (TCGA-LAML) cohort (n = 83) provided comprehensive multi-omics data including DNA methylation profiles (Illumina 450K platform), RNA sequencing (mRNA, lncRNA, and miRNA), and somatic mutation profiles. The BEAT (n = 649), TARGET (n = 156), GSE12417 (n = 79), and GSE37642 (n = 136) cohorts contributed transcriptome data. Molecular subtypes were identified using empirical Bayes-based clustering on the TCGA cohort. LSC17 scores were calculated using a validated 17-gene expression signature. A random survival forest model was developed integrating molecular features with LSC17 scores, validated across all cohorts. Immune microenvironment analysis employed multiple deconvolution methods (ESTIMATE, CIBERSORT, xCell) and pathway analysis (GSVA, GSEA). Drug sensitivity was predicted using the pRRophetic algorithm with GDSC database reference. Results: Multi-omics integration revealed two molecularly distinct AML subtypes with significant survival differences (CS2 vs CS1, P

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0324380

DOI: 10.1371/journal.pone.0324380

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