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Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia

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...

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Autores principales: Song, Ying, Tian, Shufang, Zhang, Ping, Zhang, Nan, Shen, Yan, Deng, Jianchuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803125/
https://www.ncbi.nlm.nih.gov/pubmed/35111195
http://dx.doi.org/10.3389/fgene.2021.708699
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author Song, Ying
Tian, Shufang
Zhang, Ping
Zhang, Nan
Shen, Yan
Deng, Jianchuan
author_facet Song, Ying
Tian, Shufang
Zhang, Ping
Zhang, Nan
Shen, Yan
Deng, Jianchuan
author_sort Song, Ying
collection PubMed
description 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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spelling pubmed-88031252022-02-01 Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia Song, Ying Tian, Shufang Zhang, Ping Zhang, Nan Shen, Yan Deng, Jianchuan Front Genet Genetics 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. Frontiers Media S.A. 2022-01-17 /pmc/articles/PMC8803125/ /pubmed/35111195 http://dx.doi.org/10.3389/fgene.2021.708699 Text en Copyright © 2022 Song, Tian, Zhang, Zhang, Shen and Deng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Song, Ying
Tian, Shufang
Zhang, Ping
Zhang, Nan
Shen, Yan
Deng, Jianchuan
Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia
title Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia
title_full Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia
title_fullStr Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia
title_full_unstemmed Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia
title_short Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia
title_sort construction and validation of a novel ferroptosis-related prognostic model for acute myeloid leukemia
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803125/
https://www.ncbi.nlm.nih.gov/pubmed/35111195
http://dx.doi.org/10.3389/fgene.2021.708699
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