Abstract
Purpose: This study aims to reveal the relationship between RNA N6-methyladenosine (m6A) regulators and tumor immune microenvironment (TME) in breast cancer, and to establish a risk model for predicting the occurrence and development of tumors. Patients and methods: In the present study, we respectively downloaded the transcriptome dataset of breast cancer from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database to analyze the mutation characteristics of m6A regulators and their expression profile in different clinicopathological groups. Then we used the weighted correlation network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), and cox regression to construct a risk prediction model based on m6A-associated hub genes. In addition, Immune infiltration analysis and gene set enrichment analysis (GSEA) was used to evaluate the immune cell context and the enriched gene sets among the subgroups. Results: Compared with adjacent normal tissue, differentially expressed 24 m6A regulators were identified in breast cancer. According to the expression features of m6A regulators above, we established two subgroups of breast cancer, which were also surprisingly distinguished by the feature of the immune microenvironment. The Model based on modification patterns of m6A regulators could predict the patient’s T stage and evaluate their prognosis. Besides, the low m6aRiskscore group presents an immune-activated phenotype as well as a lower tumor mutation load, and its 5-years survival rate was 90.5%, while that of the high m6ariskscore group was only 74.1%. Finally, the cohort confirmed that age (p < 0.001) and m6aRiskscore (p < 0.001) are both risk factors for breast cancer in the multivariate regression. Conclusion: The m6A regulators play an important role in the regulation of breast tumor immune microenvironment and is helpful to provide guidance for clinical immunotherapy.
Highlights
As a highly heterogeneous with complex histological characteristics and genetic features, breast cancer ranks first cancer in women on a global scale, and immunotherapy is currently a promising therapeutic strategy for advanced breast cancer (Emens, 2018)
This study aims to reveal the relationship between RNA N6-methyladenosine (m6A) regulators and tumor immune microenvironment (TME) in breast cancer, and to establish a risk model for predicting the occurrence and development of tumors
The m6A regulators play an important role in the regulation of breast tumor immune microenvironment and is helpful to provide guidance for clinical immunotherapy
Summary
As a highly heterogeneous with complex histological characteristics and genetic features, breast cancer ranks first cancer in women on a global scale, and immunotherapy is currently a promising therapeutic strategy for advanced breast cancer (Emens, 2018). Increasing researchers have come to demonstrate that dysfunction in m6A modification could affect the phenotype of tumor cells in breast cancer, colorectal cancer, and other cancers (Deng et al, 2019; Niu et al, 2019; Yang et al, 2020). He Chuan et al reported that YTHDF3 induces the translation of m6A-Enriched key brain metastatic genes to promote BC brain metastasis (Chang et al, 2020). The RNA information modified by m6A regulators needs to be recognized by the RNA binding protein (“readers”), composed of LRPPRC, HNRNPA2B1, FMR1, IGF2BP1/2/3, HNRNPC, ELAVL1, YTHDC1/2, and YTHDF1/2/3 so as to participate in downstream RNA translation and degradation processes (Yang et al, 2018; He et al, 2019)
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