Dissecting the Role of N6-Methylandenosine-Related Long Non-coding RNAs Signature in Prognosis and Immune Microenvironment of Breast Cancer.

Jinguo Zhang,Jie Dong,Qingqing Sun,Xinghua Han,Qiong Zhou,Benjie Shan,Jian Chen,Lin Lin

doi:10.3389/fcell.2021.711859

Abstract

Breast cancer (BC) represents a molecularly and clinically heterogeneous disease. Recent progress in immunotherapy has provided a glimmer of hope for several BC subtypes. The relationship between N6-methyladenosine (m6A) modification and long non-coding RNAs (LncRNAs) is still largely unexplored in BC. Here, with the intention to dissect the landscape of m6A-related lncRNAs and explore the immunotherapeutic value of the m6A-related lncRNA signature, we identified m6A-related lncRNAs by co-expression analysis from The Cancer Genome Atlas (TCGA) and stratified BC patients into different subgroups. Furthermore, we generated an m6A-related lncRNA prognostic signature. Four molecular subtypes were identified by consensus clustering. Cluster 3 preferentially had favorable prognosis, upregulated immune checkpoint expression, and high level of immune cell infiltration. Twenty-one m6A-related lncRNAs were applied to construct the m6A-related lncRNA model (m6A-LncRM). Survival analysis and receiver operating characteristic (ROC) curves further confirmed the prognostic value and prediction performance of m6A-LncRM. Finally, high- and low-risk BC subgroups displayed significantly different clinical features and immune cell infiltration status. Overall, our study systematically explored the prognostic value of the m6A-related LncRNAs and identified a high immunogenicity BC subtype. The proposed m6A-related LncRNA model might serve as a robust prognostic signature and attractive immunotherapeutic targets for BC treatment.

Highlights

The Global Cancer Statistics reported that female breast cancer (BC) surpassed lung cancer as the most diagnosed cancer, with an estimated 2.3 million new cases (11.7%) (Sung et al, 2021)
The forest plot displayed that 51 m6A-related long non-coding RNAs (lncRNAs) were significantly associated with the overall survival (OS) of BC patients (Figure 1B)
A heatmap plot compared the expression of 51 m6A-related lncRNAs for The Cancer Genome Atlas (TCGA) BC tissues versus normal tissues, and we found that all prognostic lncRNAs were abnormally expressed in BC (Figure 1C)

Summary

Introduction

The Global Cancer Statistics reported that female breast cancer (BC) surpassed lung cancer as the most diagnosed cancer, with an estimated 2.3 million new cases (11.7%) (Sung et al, 2021). BC is generally regarded as a heterogeneous disease in terms of its molecular features, histological composition, and clinical characteristics (McCart Reed et al, 2021; Sadeghalvad et al, 2021). With the evolution of high-throughput technologies, we tend to subtype the disease into clinically relevant molecular subtypes, including normal-like, luminal A and B, HER2-enriched, and basallike or more intrinsic subtypes (Ochoa et al, 2020; Morgan et al, 2021). The five clinically molecular m6A-Related LncRNAs Signature in Breast Cancer subtypes have drastically different treatment selection, prognosis, and tumor biology (Zubair et al, 2020). The subtyping of BC remains unexplored and challenging, which manifests as a heterogeneity of therapeutic responses and prognosis within the same clinical subtypes

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