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.
Highlights
Acute myeloid leukemia (AML) is one of the most aggressive hematological malignancies, with the highest incidence in adults (Short et al, 2018)
Seven m6A-related long noncoding RNAs (lncRNAs) were identified as a prognostic signature
Recent research has revealed that the inactivation of m6A RNA methylases and demethylases in AML suppresses malignant cells through multiple m6A-dependent mechanisms. m6A RNA methylases METTL3/14 (Vu et al, 2017; Weng et al, 2018) and demethylases FTO/ALKBH5 (Huang et al, 2019; Shen et al, 2020), which are aberrantly expressed in specific leukemia subtypes, play a critical role in leukemogenesis by regulating specific gene targets and signaling pathways
Summary
Acute myeloid leukemia (AML) is one of the most aggressive hematological malignancies, with the highest incidence in adults (Short et al, 2018). Recent research has revealed that the inactivation of m6A RNA methylases and demethylases in AML suppresses malignant cells through multiple m6A-dependent mechanisms. M6A RNA methylases METTL3/14 (Vu et al, 2017; Weng et al, 2018) and demethylases FTO/ALKBH5 (Huang et al, 2019; Shen et al, 2020), which are aberrantly expressed in specific leukemia subtypes, play a critical role in leukemogenesis by regulating specific gene targets and signaling pathways. Acute myeloid leukemia (AML) remains the most common type of hematopoietic malignancy in adults and has an unfavorable outcome. We aimed to construct an N6methylandenosine (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
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