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Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia

BACKGROUND: Acute myelogenous leukemia (AML) is a common and fatal disease in hematology with frequent relapses and a poor prognosis. Pyroptosis, a programmed cell death mediated by inflammasomes, has been shown to be associated with leukemia recently. However, the role of pyroptosis for diagnosis a...

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Autores principales: Liu, Songyang, Luo, Dongmei, Luo, Jie, Liang, Hanyin, Zhi, Yunfei, Wang, Dong, Xu, Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926015/
https://www.ncbi.nlm.nih.gov/pubmed/35308573
http://dx.doi.org/10.2147/IJGM.S352062
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author Liu, Songyang
Luo, Dongmei
Luo, Jie
Liang, Hanyin
Zhi, Yunfei
Wang, Dong
Xu, Na
author_facet Liu, Songyang
Luo, Dongmei
Luo, Jie
Liang, Hanyin
Zhi, Yunfei
Wang, Dong
Xu, Na
author_sort Liu, Songyang
collection PubMed
description BACKGROUND: Acute myelogenous leukemia (AML) is a common and fatal disease in hematology with frequent relapses and a poor prognosis. Pyroptosis, a programmed cell death mediated by inflammasomes, has been shown to be associated with leukemia recently. However, the role of pyroptosis for diagnosis and prognosis in AML remained less understood. METHODS: We downloaded three public datasets and constructed a signature of TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model to predict the overall survival of AML patients. Samples from the GEO database were treated as a validation cohort. Gone through LASSO-Cox regression analysis, an 8-PRG-related signature was developed. Used the median score from the signature, we classified patients in two subgroups. Subsequently, we employed univariate COX, multivariate Cox regression, ROC analysis and constructed a nomogram, Finally, differential analysis, GO and KEGG functional analysis, ESTIMATE algorithm and CIBERSORT algorithm were used to explore the difference between two groups. RESULTS: The expression levels of 90.9% pyroptosis-related genes (PRGs) had significant difference compared AML with normal tissues. The results of univariate COX regression analysis demonstrated 10 differentially expressed genes (DEGs) were associated with patients’ OS (p < 0.05). Then, we found OS of patients in the low-risk group was more likely to be lengthened compared with their high-risk counterparts (P < 0.05 both in the TCGA and GEO cohort). After controlling clinical factors, the risk score could still remain an independent predictive element (HR > 1, P < 0.001) of OS in multivariate Cox regression analysis. Furthermore, a nomogram with prognostic value for AML was thus established. Time-dependent ROC analysis proved the predictive power of the signature. Functional analysis suggested that DEGs were mainly concentrated in immune-related pathways, such as humoral immune response and T cell proliferation. TME scores and risk scores were strongly correlated and immune status differed between the risk subgroups. CONCLUSION: A novel PRG-related signature was established to forecast the prognosis in AML, and pyroptosis may be a potential therapeutic target for AML.
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spelling pubmed-89260152022-03-17 Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia Liu, Songyang Luo, Dongmei Luo, Jie Liang, Hanyin Zhi, Yunfei Wang, Dong Xu, Na Int J Gen Med Original Research BACKGROUND: Acute myelogenous leukemia (AML) is a common and fatal disease in hematology with frequent relapses and a poor prognosis. Pyroptosis, a programmed cell death mediated by inflammasomes, has been shown to be associated with leukemia recently. However, the role of pyroptosis for diagnosis and prognosis in AML remained less understood. METHODS: We downloaded three public datasets and constructed a signature of TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model to predict the overall survival of AML patients. Samples from the GEO database were treated as a validation cohort. Gone through LASSO-Cox regression analysis, an 8-PRG-related signature was developed. Used the median score from the signature, we classified patients in two subgroups. Subsequently, we employed univariate COX, multivariate Cox regression, ROC analysis and constructed a nomogram, Finally, differential analysis, GO and KEGG functional analysis, ESTIMATE algorithm and CIBERSORT algorithm were used to explore the difference between two groups. RESULTS: The expression levels of 90.9% pyroptosis-related genes (PRGs) had significant difference compared AML with normal tissues. The results of univariate COX regression analysis demonstrated 10 differentially expressed genes (DEGs) were associated with patients’ OS (p < 0.05). Then, we found OS of patients in the low-risk group was more likely to be lengthened compared with their high-risk counterparts (P < 0.05 both in the TCGA and GEO cohort). After controlling clinical factors, the risk score could still remain an independent predictive element (HR > 1, P < 0.001) of OS in multivariate Cox regression analysis. Furthermore, a nomogram with prognostic value for AML was thus established. Time-dependent ROC analysis proved the predictive power of the signature. Functional analysis suggested that DEGs were mainly concentrated in immune-related pathways, such as humoral immune response and T cell proliferation. TME scores and risk scores were strongly correlated and immune status differed between the risk subgroups. CONCLUSION: A novel PRG-related signature was established to forecast the prognosis in AML, and pyroptosis may be a potential therapeutic target for AML. Dove 2022-03-12 /pmc/articles/PMC8926015/ /pubmed/35308573 http://dx.doi.org/10.2147/IJGM.S352062 Text en © 2022 Liu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Liu, Songyang
Luo, Dongmei
Luo, Jie
Liang, Hanyin
Zhi, Yunfei
Wang, Dong
Xu, Na
Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia
title Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia
title_full Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia
title_fullStr Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia
title_full_unstemmed Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia
title_short Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia
title_sort construction of a pyroptosis-related signature for prognostic prediction and characterization of immune microenvironment in acute myelogenous leukemia
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926015/
https://www.ncbi.nlm.nih.gov/pubmed/35308573
http://dx.doi.org/10.2147/IJGM.S352062
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