AUTHOR=Xue Jia , Chen Haoran , Lu Jinqi , Zhang Haojun , Geng Jie , He Peifeng , Lu Xuechun 

TITLE=Identification of immunity-related lncRNAs and construction of a ceRNA network of potential prognostic biomarkers in acute myeloid leukemia

JOURNAL=Frontiers in Genetics

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1203345

DOI=10.3389/fgene.2023.1203345

ISSN=1664-8021

ABSTRACT=Objectives: Using bioinformatics analyses, this study aimed to identify lncRNAs related to the immune status of acute myeloid leukemia (AML) patients, and to ascertain potential impact in immunity-related ceRNA networks on AML prognosis. 
Methods: AML-related RNA-Seq FPKM data, AML-related miRNA expression microarray data, and gene sets associated with immunity-related pathways were respectively obtained from the TCGA, GEO, and ImmReg databases. An immunity-related ceRNA network was then constructed according to predicted interactions between AML-related mRNAs, lncRNAs, and miRNAs. After performing LASSO and multivariable Cox regression analyses, lncRNAs in the ceRNA network were used to establish an AML prognostic model. According to mutual regulatory relationships and consistent trends of expression among candidate ceRNAs, two ceRNA subnetworks related to the AML prognostic model were determined. Finally, the correlation between expression levels of mRNAs, lncRNAs, and miRNAs in each ceRNA subnetwork and immune cell infiltration (assessed by combining the ESTIMATE and CIBERSORT methods and ssGSEA) were analyzed. 
Results: A total of 424 immunity-related differentially expressed (IR-DE) mRNAs (IR-DEmRNAs), 191 IR-DElncRNAs, and 69 IR-DEmiRNAs were obtained, and a ceRNA network of 20 IR-DElncRNAs, 6 IR-DEmRNAs, and 3 IR-DEmiRNAs was established. Univariable Cox regression analysis was conducted on the 20 IR-DElncRNAs, and 7 of which were identified to be significantly correlated with the overall survival (OS) time of AML patients. Then, two IR-DElncRNAs (MEG3 and HCP5) were screened as independent OS-related factors by LASSO and multivariable Cox regression analyses and construct prognostic model to evaluate survival risk in AML patients. Survival analyses indicated that OS of patients was often poor in the high-risk group. Additionally, from this model, two ceRNA regulatory pathways potentially involved in immune regulation of AML prognosis were identified: MEG3/miR⁃125a⁃5p/SEMA4C and HCP5/miR⁃125b⁃5p/IL6R.
Conclusion: The lncRNAs HCP5 and MEG3 may act as key ceRNAs in the pathogenesis in AML by regulating immune cell representation as part of regulatory lncRNA-miRNA-mRNA axes. The candidate mRNAs, lncRNAs, and miRNAs included in the ceRNA network identified herein may serve as useful prognostic biomarkers and immunotherapeutic targets for AML.