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...

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Autores principales: Ding Li, Jiaming Liang, Cheng Cheng, Wenbin Guo, Shuolei Li, Wenping Song, Zhenguo Song, Yongtao Bai, Yongna Zhang, Xuan Wu, Wenzhou Zhang
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:b4680e319ef0403ebee2cc08c02b820f2021-11-16T07:47:25ZIdentification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia2296-634X10.3389/fcell.2021.770451https://doaj.org/article/b4680e319ef0403ebee2cc08c02b820f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.770451/fullhttps://doaj.org/toc/2296-634XBackground: 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.Ding LiJiaming LiangCheng ChengWenbin GuoShuolei LiWenping SongZhenguo SongYongtao BaiYongna ZhangXuan WuWenzhou ZhangFrontiers Media S.A.articleM6Along noncoding RNAprognostic signatureimmunotherapy responseacute myeloid leukemiaBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution DOAJ
collection DOAJ
language EN
topic M6A
long noncoding RNA
prognostic signature
immunotherapy response
acute myeloid leukemia
Biology (General)
QH301-705.5
spellingShingle M6A
long noncoding RNA
prognostic signature
immunotherapy response
acute myeloid leukemia
Biology (General)
QH301-705.5
Ding Li
Jiaming Liang
Cheng Cheng
Wenbin Guo
Shuolei Li
Wenping Song
Zhenguo Song
Yongtao Bai
Yongna Zhang
Xuan Wu
Wenzhou Zhang
Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia
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 article
author Ding Li
Jiaming Liang
Cheng Cheng
Wenbin Guo
Shuolei Li
Wenping Song
Zhenguo Song
Yongtao Bai
Yongna Zhang
Xuan Wu
Wenzhou Zhang
author_facet Ding Li
Jiaming Liang
Cheng Cheng
Wenbin Guo
Shuolei Li
Wenping Song
Zhenguo Song
Yongtao Bai
Yongna Zhang
Xuan Wu
Wenzhou Zhang
author_sort Ding Li
title 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_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_sort identification of m6a-related lncrnas associated with prognoses and immune responses in acute myeloid leukemia
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/b4680e319ef0403ebee2cc08c02b820f
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