Frontiers in Genetics (Jan 2022)
Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia
Abstract
Acute myeloid leukemia (AML) is a clonal malignant proliferative blood disorder with a poor prognosis. Ferroptosis, a novel form of programmed cell death, holds great promise for oncology treatment, and has been demonstrated to interfere with the development of various diseases. A range of genes are involved in regulating ferroptosis and can serve as markers of it. Nevertheless, the prognostic significance of these genes in AML remains poorly understood. Transcriptomic and clinical data for AML patients were acquired from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Univariate Cox analysis was performed to identify ferroptosis-related genes with prognostic value, and the least absolute shrinkage and selection operator (LASSO) algorithm and stepwise multivariate Cox regression analysis were utilized to optimize gene selection from the TCGA cohort (132 samples) for model construction. Tumor samples from the GEO database (136 samples and 104 samples) were used as validation groups to estimate the predictive performance of the risk model. Finally, an eight-gene prognostic signature (including CHAC1, CISD1, DPP4, GPX4, AIFM2, SQLE, PGD, and ACSF2) was identified for the prediction of survival probability and was used to stratify AML patients into high- and low-risk groups. Survival analysis illustrated significantly prolonged overall survival and lower mortality in the low-risk group. The area under the receiver operating characteristic curve demonstrated good results for the training set (1-year: 0.846, 2-years: 0.826, and 3-years: 0.837), which verified the accuracy of the model for predicting patient survival. Independent prognostic analysis indicated that the model could be used as a prognostic factor (p ≤ 0.001). Functional enrichment analyses revealed underlying mechanisms and notable differences in the immune status of the two risk groups. In brief, we conducted and validated a novel ferroptosis-related prognostic model for outcome prediction and risk stratification in AML, with great potential to guide individualized treatment strategies in the future.
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