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Published on: December 13, 2018
m6A-related lncRNAs predict prognosis and indicate immune microenvironment in acute myeloid leukemia
Fangmin Zhong1,2, Fangyi Yao1, Ying Cheng1
1Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006, Jiangxi, China.
Abstract:
Acute myeloid leukemia (AML) is a complex hematologic malignancy. Survival rate of AML patients is low. N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in AML tumorigenesis and progression. However, the relationship between lncRNAs and biological characteristics of AML, as well as how lncRNAs influence the prognosis of AML patients, remain unclear. In this study. In this study, Pearson correlation analysis was used to identify lncRNAs related to m6A regulatory genes, namely m6A-related lncRNAs. And we analyzed their roles and prognostic values in AML. m6A-related lncRNAs associated with patient prognosis were screened using univariate Cox regression analysis, followed by systematic analysis of the relationship between these genes and AML clinicopathologic and biologic characteristics. Furthermore, we examined the characteristics of tumor immune microenvironment (TIME) using different IncRNA clustering models. Using LASSO regression, we identified the risk signals related to prognosis of AML patients. We then constructed and verified a risk model based on m6A-related lncRNAs for independent prediction of overall survival in AML patients. Our results indicate that risk scores, calculated based on risk-related signaling, were related to the clinicopathologic characteristics of AML and level of immune infiltration. Finally, we examined the expression level of TRAF3IP2-AS1 in patient samples through real-time polymerase chain reaction analysis and in GEO datasets, and we identified a interaction relationship between SRSF10 and TRAF3IP2-AS1 through in vitro assays. Our study shows that m6A-related lncRNAs, evaluated using the risk prediction model, can potentially be used to predict prognosis and design immunotherapy in AML patients.
Insights
This study identifies N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) that predict prognosis in acute myeloid leukemia (AML). A novel risk model using these m6A-related lncRNAs can aid in predicting AML patient survival and guiding immunotherapy strategies.
Area of Science:
- Hematologic Malignancies
- Molecular Oncology
- Cancer Genomics
Background:
- Acute myeloid leukemia (AML) has a low survival rate, with N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) implicated in its development.
- The precise roles of lncRNAs in AML biology and their impact on patient outcomes remain incompletely understood.
Purpose of the Study:
- To identify m6A-related lncRNAs (m6A-lncRNAs) in AML.
- To analyze the prognostic value and biological significance of these m6A-lncRNAs.
- To develop a predictive model for AML patient survival and immune microenvironment characteristics.
Main Methods:
- Pearson correlation analysis to identify m6A-lncRNAs.
- Univariate Cox regression for prognostic screening.
- LASSO regression to build a risk prediction model.
- Analysis of tumor immune microenvironment (TIME) and clinicopathologic features.
- Validation of TRAF3IP2-AS1 expression and interaction with SRSF10.
Main Results:
- Identified m6A-lncRNAs associated with AML prognosis.
- Developed and validated a risk model based on m6A-lncRNAs for predicting overall survival.
- Risk scores correlated with AML clinicopathologic features and immune infiltration levels.
- TRAF3IP2-AS1 expression and its interaction with SRSF10 were observed.
Conclusions:
- m6A-related lncRNAs offer potential as prognostic biomarkers in AML.
- The developed risk model can independently predict AML patient survival.
- These findings may inform the design of targeted immunotherapies for AML.
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