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Expression pattern of m6A regulators is significantly correlated with malignancy and antitumor immune response of breast cancer

Cancer Gene Therapy volume 28, pages 188–196 (2021)Cite this article

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Abstract

More than 24 regulators have been revealed to dynamically participant in N6-methyladenosine (m6A) RNA methylation, and play critical roles in tumorigenesis and development of cancers. However, their functional roles have not been comprehensively clarified in breast cancer. Here we systematically analyzed the RNA sequencing data of 24 main m6A RNA methylation regulators in 775 breast cancer patients from The Cancer Genome Atlas dataset. Consensus clustering of the 24 m6A regulators was carried out and identified two patient subgroups, RNA methylation 1/2 (RM1/2). RM1 demonstrated generally lower RNA methylation modification than that of RM2, and had significantly shorter overall survival. The hallmarks of PI3K/AKT signaling in cancer, KRAS signaling and angiogenesis were significantly enriched in RM1. Moreover, the association between m6A regulators and antitumor immune response was also investigated in this study and revealed that RM2 was associated with significantly higher expressions of HLA-A, higher numbers of tumor-infiltrating CD8+ T cells, helper T cells and activated NK cells, but lower expressions of PD-L1, PD-L2, TIM3, and CCR4 than RM1. In conclusion, the expression pattern of m6A regulators was significantly correlated with the malignancy, prognosis and antitumor immune response in breast cancer, which might serve as potential targets and biomarkers for immunotherapy.

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Fig. 1: Expression pattern of m6A regulators in breast cancer across different clinicopathological features.
Fig. 2: Differential overall survivals of breast cancer patients in RM1/2 subgroups.
Fig. 3: Functional annotation of differentially expressed genes in RM1/2 subgroups.
Fig. 4: Immune cell infiltration, expressions of antigen presenting genes, and immunomodulator genes in RM1/2 subgroups.

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Acknowledgements

We gratefully acknowledge Jean J. Zhao (Dana Farber Cancer Institute, Boston, Massachusetts, USA) for her suggestion in revising the paper, and the contributions from TCGA, TCIA, and CIBERSORT networks.

Funding

This work was supported by National Natural Science Foundation of China (81201747), Natural Science Foundation of Guangdong Province, China (S2012040006323, 2014A030313023), and the open Foundation of State Key Laboratory of Oncology in South China (HN2013-07).

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Author notes

  1. These authors contributed equally: Xiaofang He, Liqiang Tan

Authors and Affiliations

  1. Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, China

    Xiaofang He & Guoping Shen

  2. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA

    Xiaofang He & Jing Ni

  3. Department of Medical Bioinformatics, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, China

    Liqiang Tan

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  1. Xiaofang He
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Correspondence to Guoping Shen.

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He, X., Tan, L., Ni, J. et al. Expression pattern of m6A regulators is significantly correlated with malignancy and antitumor immune response of breast cancer. Cancer Gene Ther 28, 188–196 (2021). https://doi.org/10.1038/s41417-020-00208-1

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