Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia

Abstract

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.

Comprehensive Analysis of N6-Methyladenosine-Related Long Noncoding RNA Prognosis of Acute Myeloid Leukemia and Immune Cell Infiltration

“…The other six lncRNAs were rarely reported in cancers and further research should be conducted to reveal their potential role in AML development. Interestingly, seven lncRNAs were screened in a study to identify m6A-related lncRNAs for prognosis in adult AML ( Li et al, 2021 ). Since the population we used was pediatric AML patients, this may have led to different results from ours.…”

A Distinct Glucose Metabolism Signature of Lung Adenocarcinoma With Prognostic Value

“…We constructed a nomogram based on the clinical stage, T stage, and the signature score using the R package “rms.” To assess the application of the nomogram, the R package “ROCsurvival” was performed to construct ROC curves to predict the 1-, 3-, and 5-year OS by the nomogram. The R package “rms” was used to construct calibration curves to assess the accuracy for the prediction of 1-, 3-, and 5-year OS prediction ( Li et al, 2021 ).…”

One Stone, Two Birds: N6-Methyladenosine RNA Modification in Leukemia Stem Cells and the Tumor Immune Microenvironment in Acute Myeloid Leukemia

“…In brief, m 6 A modification plays significant roles in regulating the TIME and affecting immunotherapy efficacy. m 6 A-related long noncoding RNAs (lncRNAs) are reported to influence the immune response in AML ( 118 ). It can be assumed that m 6 A indirectly modulates the immune response by interacting with lncRNAs.…”