Cargando…
Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia
Background: Acute myeloid leukemia (AML) remains the most common type of hematopoietic malignancy in adults and has an unfavorable outcome. Herein, we aimed to construct an N6-methylandenosine (m6A)-related long noncoding RNAs (lncRNAs) signature to accurately predict the prognosis of patients with...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637120/ https://www.ncbi.nlm.nih.gov/pubmed/34869365 http://dx.doi.org/10.3389/fcell.2021.770451 |
_version_ | 1784608678076219392 |
---|---|
author | Li, Ding Liang, Jiaming Cheng, Cheng Guo, Wenbin Li, Shuolei Song, Wenping Song, Zhenguo Bai, Yongtao Zhang, Yongna Wu, Xuan Zhang, Wenzhou |
author_facet | Li, Ding Liang, Jiaming Cheng, Cheng Guo, Wenbin Li, Shuolei Song, Wenping Song, Zhenguo Bai, Yongtao Zhang, Yongna Wu, Xuan Zhang, Wenzhou |
author_sort | Li, Ding |
collection | PubMed |
description | Background: Acute myeloid leukemia (AML) remains the most common type of hematopoietic malignancy in adults and has an unfavorable outcome. Herein, we aimed to construct an N6-methylandenosine (m6A)-related long noncoding RNAs (lncRNAs) signature to accurately predict the prognosis of patients with AML using the data downloaded from The Cancer Genome Atlas (TCGA) database. Methods: The RNA-seq and clinical data were obtained from the TCGA AML cohort. First, Pearson correlation analysis was performed to identify the m6A-related lncRNAs. Next, univariate Cox regression analysis was used to determine the candidate lncRNAs with prognostic value. Then, feature selection was carried out by Least absolute shrinkage and selection operator (LASSO) analysis, and seven eligible m6A-related lncRNAs were included to construct the prognostic risk signature. Kaplan–Meier and receiver operating characteristic (ROC) curve analyses were performed to evaluate the predictive capacity of the risk signature both in the training and testing datasets. A nomogram was used to predict 1-year, 2-year, and 3-year overall survival (OS) of AML patients. Next, the expression levels of lncRNAs in the signature were validated in AML samples by qRT-PCR. Functional enrichment analyses were carried out to identify probable biological processes and cellular pathways. The ceRNA network was developed to explore the downstream targets and mechanisms of m6A-related lncRNAs in AML. Results: Seven m6A-related lncRNAs were identified as a prognostic signature. The low-risk group hold significantly prolonged OS. The nomogram showed excellent accuracy of the signature for predicting 1-year, 2-year and 3-year OS (AUC = 0.769, 0.820, and 0.800, respectively). Moreover, the risk scores were significantly correlated with enrichment in cancer hallmark- and malignancy-related pathways and immunotherapy response in AML patients. Conclusion: We developed and validated a novel risk signature with m6A-related lncRNAs which could predict prognosis accurately and reflect the immunotherapy response in AML patients. |
format | Online Article Text |
id | pubmed-8637120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86371202021-12-03 Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia Li, Ding Liang, Jiaming Cheng, Cheng Guo, Wenbin Li, Shuolei Song, Wenping Song, Zhenguo Bai, Yongtao Zhang, Yongna Wu, Xuan Zhang, Wenzhou Front Cell Dev Biol Cell and Developmental Biology Background: Acute myeloid leukemia (AML) remains the most common type of hematopoietic malignancy in adults and has an unfavorable outcome. Herein, we aimed to construct an N6-methylandenosine (m6A)-related long noncoding RNAs (lncRNAs) signature to accurately predict the prognosis of patients with AML using the data downloaded from The Cancer Genome Atlas (TCGA) database. Methods: The RNA-seq and clinical data were obtained from the TCGA AML cohort. First, Pearson correlation analysis was performed to identify the m6A-related lncRNAs. Next, univariate Cox regression analysis was used to determine the candidate lncRNAs with prognostic value. Then, feature selection was carried out by Least absolute shrinkage and selection operator (LASSO) analysis, and seven eligible m6A-related lncRNAs were included to construct the prognostic risk signature. Kaplan–Meier and receiver operating characteristic (ROC) curve analyses were performed to evaluate the predictive capacity of the risk signature both in the training and testing datasets. A nomogram was used to predict 1-year, 2-year, and 3-year overall survival (OS) of AML patients. Next, the expression levels of lncRNAs in the signature were validated in AML samples by qRT-PCR. Functional enrichment analyses were carried out to identify probable biological processes and cellular pathways. The ceRNA network was developed to explore the downstream targets and mechanisms of m6A-related lncRNAs in AML. Results: Seven m6A-related lncRNAs were identified as a prognostic signature. The low-risk group hold significantly prolonged OS. The nomogram showed excellent accuracy of the signature for predicting 1-year, 2-year and 3-year OS (AUC = 0.769, 0.820, and 0.800, respectively). Moreover, the risk scores were significantly correlated with enrichment in cancer hallmark- and malignancy-related pathways and immunotherapy response in AML patients. Conclusion: We developed and validated a novel risk signature with m6A-related lncRNAs which could predict prognosis accurately and reflect the immunotherapy response in AML patients. Frontiers Media S.A. 2021-11-16 /pmc/articles/PMC8637120/ /pubmed/34869365 http://dx.doi.org/10.3389/fcell.2021.770451 Text en Copyright © 2021 Li, Liang, Cheng, Guo, Li, Song, Song, Bai, Zhang, Wu and Zhang. 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 | Cell and Developmental Biology Li, Ding Liang, Jiaming Cheng, Cheng Guo, Wenbin Li, Shuolei Song, Wenping Song, Zhenguo Bai, Yongtao Zhang, Yongna Wu, Xuan Zhang, Wenzhou Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia |
title | Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia |
title_full | Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia |
title_fullStr | Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia |
title_full_unstemmed | Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia |
title_short | Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia |
title_sort | identification of m6a-related lncrnas associated with prognoses and immune responses in acute myeloid leukemia |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637120/ https://www.ncbi.nlm.nih.gov/pubmed/34869365 http://dx.doi.org/10.3389/fcell.2021.770451 |
work_keys_str_mv | AT liding identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia AT liangjiaming identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia AT chengcheng identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia AT guowenbin identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia AT lishuolei identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia AT songwenping identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia AT songzhenguo identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia AT baiyongtao identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia AT zhangyongna identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia AT wuxuan identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia AT zhangwenzhou identificationofm6arelatedlncrnasassociatedwithprognosesandimmuneresponsesinacutemyeloidleukemia |