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Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia

BACKGROUND: Obesity confers enhanced risk for multiple diseases including cancer. The DNA methylation alterations in obesity-related genes have been implicated in several human solid tumors. However, the underlying role and clinical implication of DNA methylation of obesity-related genes in acute my...

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Autores principales: Zhang, Ting-juan, Xu, Zi-jun, Gu, Yu, Ma, Ji-chun, Wen, Xiang-mei, Zhang, Wei, Deng, Zhao-qun, Qian, Jun, Lin, Jiang, Zhou, Jing-dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824952/
https://www.ncbi.nlm.nih.gov/pubmed/33485366
http://dx.doi.org/10.1186/s13148-021-01013-9
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author Zhang, Ting-juan
Xu, Zi-jun
Gu, Yu
Ma, Ji-chun
Wen, Xiang-mei
Zhang, Wei
Deng, Zhao-qun
Qian, Jun
Lin, Jiang
Zhou, Jing-dong
author_facet Zhang, Ting-juan
Xu, Zi-jun
Gu, Yu
Ma, Ji-chun
Wen, Xiang-mei
Zhang, Wei
Deng, Zhao-qun
Qian, Jun
Lin, Jiang
Zhou, Jing-dong
author_sort Zhang, Ting-juan
collection PubMed
description BACKGROUND: Obesity confers enhanced risk for multiple diseases including cancer. The DNA methylation alterations in obesity-related genes have been implicated in several human solid tumors. However, the underlying role and clinical implication of DNA methylation of obesity-related genes in acute myeloid leukemia (AML) has yet to be elucidated. RESULTS: In the discovery stage, we identified that DNA methylation-associated LEP expression was correlated with prognosis among obesity-related genes from the databases of The Cancer Genome Atlas. In the validation stage, we verified that LEP hypermethylation was a frequent event in AML by both targeted bisulfite sequencing and real-time quantitative methylation-specific PCR. Moreover, LEP hypermethylation, correlated with reduced LEP expression, was found to be associated with higher bone marrow blasts, lower platelets, and lower complete remission (CR) rate in AML. Importantly, survival analysis showed that LEP hypermethylation was significantly associated with shorter overall survival (OS) in AML. Moreover, multivariate analysis disclosed that LEP hypermethylation was an independent risk factor affecting CR and OS among non-M3 AML. By clinical and bioinformatics analysis, LEP may be also regulated by miR-517a/b expression in AML. CONCLUSIONS: Our findings indicated that the obesity-related gene LEP methylation is associated with LEP inactivation, and acts as an independent prognostic predictor in AML.
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spelling pubmed-78249522021-01-25 Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia Zhang, Ting-juan Xu, Zi-jun Gu, Yu Ma, Ji-chun Wen, Xiang-mei Zhang, Wei Deng, Zhao-qun Qian, Jun Lin, Jiang Zhou, Jing-dong Clin Epigenetics Research BACKGROUND: Obesity confers enhanced risk for multiple diseases including cancer. The DNA methylation alterations in obesity-related genes have been implicated in several human solid tumors. However, the underlying role and clinical implication of DNA methylation of obesity-related genes in acute myeloid leukemia (AML) has yet to be elucidated. RESULTS: In the discovery stage, we identified that DNA methylation-associated LEP expression was correlated with prognosis among obesity-related genes from the databases of The Cancer Genome Atlas. In the validation stage, we verified that LEP hypermethylation was a frequent event in AML by both targeted bisulfite sequencing and real-time quantitative methylation-specific PCR. Moreover, LEP hypermethylation, correlated with reduced LEP expression, was found to be associated with higher bone marrow blasts, lower platelets, and lower complete remission (CR) rate in AML. Importantly, survival analysis showed that LEP hypermethylation was significantly associated with shorter overall survival (OS) in AML. Moreover, multivariate analysis disclosed that LEP hypermethylation was an independent risk factor affecting CR and OS among non-M3 AML. By clinical and bioinformatics analysis, LEP may be also regulated by miR-517a/b expression in AML. CONCLUSIONS: Our findings indicated that the obesity-related gene LEP methylation is associated with LEP inactivation, and acts as an independent prognostic predictor in AML. BioMed Central 2021-01-23 /pmc/articles/PMC7824952/ /pubmed/33485366 http://dx.doi.org/10.1186/s13148-021-01013-9 Text en © The Author(s) 2021 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/. The Creative Commons Public Domain Dedication waiver (http://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
Zhang, Ting-juan
Xu, Zi-jun
Gu, Yu
Ma, Ji-chun
Wen, Xiang-mei
Zhang, Wei
Deng, Zhao-qun
Qian, Jun
Lin, Jiang
Zhou, Jing-dong
Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia
title Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia
title_full Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia
title_fullStr Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia
title_full_unstemmed Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia
title_short Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia
title_sort identification and validation of obesity-related gene lep methylation as a prognostic indicator in patients with acute myeloid leukemia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824952/
https://www.ncbi.nlm.nih.gov/pubmed/33485366
http://dx.doi.org/10.1186/s13148-021-01013-9
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