AUTHOR=Dong Menglu , Shen Wenzhuang , Yang Guang , Yang Zhifang , Li Xingrui TITLE=Analysis of m6A Methylation Modification Patterns and Tumor Immune Microenvironment in Breast Cancer JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.785058 DOI=10.3389/fcell.2022.785058 ISSN=2296-634X ABSTRACT=

Increasing evidence indicates that the abnormal expression of N6-methyladenosine (m6A) modification is closely related to the epigenetic regulation of immune response in breast cancer (BC). However, the potential roles of m6A modification in the tumor microenvironment (TME) of BC remain unclear. For addressing this issue, we comprehensively analyzed the m6A modification patterns in 983 samples and correlated these modification patterns with TME immune cell infiltration, based on 23 kinds of m6A regulators. Principal component analysis (PCA) was used to construct the m6A scoring system to quantify the modification pattern of m6A of BC individuals. Consequently, three different m6A modification patterns were identified, and the infiltrating characteristics of TME cells were consistent with the three immune phenotypes, including immune rejection, immune inflammation, and immune desert. Besides, our analysis showed that the prognosis of patients could be predicted by evaluating the m6A modification pattern in the tumor. The low m6Ascore corresponded to increased mutation burden and immune activation, while stroma activation and lack of immune infiltration were observed in high m6Ascore subtypes. In addition, a low m6Ascore was associated with enhanced response to anti-PD-1/PD-L1 immunotherapy. In conclusion, the m6A modification pattern was closely related to the BC immune landscape. This well-validated score model of the m6A modification patterns will provide a valuable tool to depict the tumor immune state and guide effective tumor immunotherapy for combating BC.