Identification of N6-Methyladenosine-Related LncRNAs for Predicting Overall Survival and Clustering of a Potentially Novel Molecular Subtype of Breast Cancer

FRONTIERS IN ONCOLOGY(2021)

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Abstract
We aimed to identify a signature comprising N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) and molecular subtypes associated with breast cancer (BRCA). We obtained data of BRCA samples from The Cancer Genome Atlas database. The m6A-related lncRNA prognostic signature (m6A-LPS) included 10 lncRNAs previously identified as prognostic m6A-related lncRNAs and was constructed using integrated bioinformatics analysis and validated. Accordingly, a risk score based on the m6A-LPS signature was established and shown to confirm differences in survival between high-risk and low-risk groups. Three distinct genotypes were identified, whose characteristics included features of the tumor immune microenvironment in each subtype. Our results indicated that patients in Cluster 2 might have a worse prognostic outcome than those in other clusters. The three genotypes and risk subgroups were enriched in different biological processes and pathways, respectively. We then constructed a competing endogenous RNA network based on the prognostic m6A-related lncRNAs. Finally, we validated the expression levels of target lncRNAs in 72 clinical samples. In summary, the m6A-LPS and the potentially novel genotype may provide a theoretical basis for further study of the molecular mechanism of BRCA and may provide novel insights into precision medicine.

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Key words
breast cancer, m6A modification, lncRNA, prognostic model, molecular subtype, tumor immune microenvironment, ceRNA network
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