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The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia

BACKGROUND: The high degree of heterogeneity brought great challenges to the diagnosis and treatment of acute myeloid leukemia (AML). Although several different AML prognostic scoring models have been proposed to assess the prognosis of patients, the accuracy still needs to be improved. As important...

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Autores principales: Zeng, Tiansheng, Cui, Longzhen, Huang, Wenhui, Liu, Yan, Si, Chaozeng, Qian, Tingting, Deng, Cong, Fu, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340489/
https://www.ncbi.nlm.nih.gov/pubmed/34348737
http://dx.doi.org/10.1186/s12916-021-02047-9
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author Zeng, Tiansheng
Cui, Longzhen
Huang, Wenhui
Liu, Yan
Si, Chaozeng
Qian, Tingting
Deng, Cong
Fu, Lin
author_facet Zeng, Tiansheng
Cui, Longzhen
Huang, Wenhui
Liu, Yan
Si, Chaozeng
Qian, Tingting
Deng, Cong
Fu, Lin
author_sort Zeng, Tiansheng
collection PubMed
description BACKGROUND: The high degree of heterogeneity brought great challenges to the diagnosis and treatment of acute myeloid leukemia (AML). Although several different AML prognostic scoring models have been proposed to assess the prognosis of patients, the accuracy still needs to be improved. As important components of the tumor microenvironment, immune cells played important roles in the physiological functions of tumors and had certain research value. Therefore, whether the tumor immune microenvironment (TIME) can be used to assess the prognosis of AML aroused our great interest. METHODS: The patients’ gene expression profile from 7 GEO databases was normalized after removing the batch effect. TIME cell components were explored through Xcell tools and then hierarchically clustered to establish TIME classification. Subsequently, a prognostic model was established by Lasso-Cox. Multiple GEO databases and the Cancer Genome Atlas dataset were employed to validate the prognostic performance of the model. Receiver operating characteristic (ROC) and the concordance index (C-index) were utilized to assess the prognostic efficacy. RESULTS: After analyzing the composition of TIME cells in AML, we found infiltration of ten types of cells with prognostic significance. Then using hierarchical clustering methods, we established a TIME classification system, which clustered all patients into three groups with distinct prognostic characteristics. Using the differential genes between the first and third groups in the TIME classification, we constructed a 121-gene prognostic model. The model successfully divided 1229 patients into the low and high groups which had obvious differences in prognosis. The high group with shorter overall survival had more patients older than 60 years and more poor-risk patients (both P< 0.001). Besides, the model can perform well in multiple datasets and could further stratify the cytogenetically normal AML patients and intermediate-risk AML population. Compared with the European Leukemia Net Risk Stratification System and other AML prognostic models, our model had the highest C-index and the largest AUC of the ROC curve, which demonstrated that our model had the best prognostic efficacy. CONCLUSION: A prognostic model for AML based on the TIME classification was constructed in our study, which may provide a new strategy for precision treatment in AML. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-021-02047-9.
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spelling pubmed-83404892021-08-06 The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia Zeng, Tiansheng Cui, Longzhen Huang, Wenhui Liu, Yan Si, Chaozeng Qian, Tingting Deng, Cong Fu, Lin BMC Med Research Article BACKGROUND: The high degree of heterogeneity brought great challenges to the diagnosis and treatment of acute myeloid leukemia (AML). Although several different AML prognostic scoring models have been proposed to assess the prognosis of patients, the accuracy still needs to be improved. As important components of the tumor microenvironment, immune cells played important roles in the physiological functions of tumors and had certain research value. Therefore, whether the tumor immune microenvironment (TIME) can be used to assess the prognosis of AML aroused our great interest. METHODS: The patients’ gene expression profile from 7 GEO databases was normalized after removing the batch effect. TIME cell components were explored through Xcell tools and then hierarchically clustered to establish TIME classification. Subsequently, a prognostic model was established by Lasso-Cox. Multiple GEO databases and the Cancer Genome Atlas dataset were employed to validate the prognostic performance of the model. Receiver operating characteristic (ROC) and the concordance index (C-index) were utilized to assess the prognostic efficacy. RESULTS: After analyzing the composition of TIME cells in AML, we found infiltration of ten types of cells with prognostic significance. Then using hierarchical clustering methods, we established a TIME classification system, which clustered all patients into three groups with distinct prognostic characteristics. Using the differential genes between the first and third groups in the TIME classification, we constructed a 121-gene prognostic model. The model successfully divided 1229 patients into the low and high groups which had obvious differences in prognosis. The high group with shorter overall survival had more patients older than 60 years and more poor-risk patients (both P< 0.001). Besides, the model can perform well in multiple datasets and could further stratify the cytogenetically normal AML patients and intermediate-risk AML population. Compared with the European Leukemia Net Risk Stratification System and other AML prognostic models, our model had the highest C-index and the largest AUC of the ROC curve, which demonstrated that our model had the best prognostic efficacy. CONCLUSION: A prognostic model for AML based on the TIME classification was constructed in our study, which may provide a new strategy for precision treatment in AML. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-021-02047-9. BioMed Central 2021-08-05 /pmc/articles/PMC8340489/ /pubmed/34348737 http://dx.doi.org/10.1186/s12916-021-02047-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Zeng, Tiansheng
Cui, Longzhen
Huang, Wenhui
Liu, Yan
Si, Chaozeng
Qian, Tingting
Deng, Cong
Fu, Lin
The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia
title The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia
title_full The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia
title_fullStr The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia
title_full_unstemmed The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia
title_short The establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia
title_sort establishment of a prognostic scoring model based on the new tumor immune microenvironment classification in acute myeloid leukemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340489/
https://www.ncbi.nlm.nih.gov/pubmed/34348737
http://dx.doi.org/10.1186/s12916-021-02047-9
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