Bioinformatics Analysis the Characteristics and Correlation of m6A Methylation in Breast Cancer Progression

Research Square (Research Square)(2021)

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Abstract
Background: RNA m6A methylation regulator has been shown to play an important regulatory role in tumorigenesis and progression. However, the role and characteristics of RNA m6A methylation in breast cancer are not yet clear. Objective: To analyze the effect of the expression pattern of M6A methylation factor on the progression of breast cancer by bioinformatics. Results: This study uses bioinformatics to analyze three data sets of TCGA-BRCA, GSE96058 and GSE25066. According to the expression level of m6A-related genes, breast cancer samples are divided into 4 subtypes: quiescent, m6A-methylation, protein-binding, and mixed. The results of R-survival analysis showed that the survival of breast cancer samples of the four subtypes was significantly different. The analysis of breast cancer gene expression features showed that there are significant differences in the number of exon skip among the four subtypes. For tumor driver genes, the degree of TP53 mutation and copy number loss are the most in the protein-binding subtype. Among DNA damage repair genes, the copy number of RAD54B in the protein binding subtype is significantly increased, while other DNA damage repair-related genes have fewer mutations and copy number deletions are common. The effect of m6A methylation on the proportion of infiltrated immune cells indicates that Macrophages M0 and Mast cells resting are significantly different in the four m6A subgroups, and are related to patient prognosis. The number of sensitive samples of chemotherapeutics (taxane anthracyclines) is the lowest in the quiescent subtype. In addition, the highest tumor stemness index in breast cancer samples is the protein-bound type, and the lowest is the m6A methylated type. Conclusion: The results of our analysis suggest that the reduced expression level of m6A methylation writer gene and the high expression of m6A reader protein in the four methylation subtypes of breast cancer are key to the progression of breast cancer.
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Key words
methylation,breast cancer progression,breast cancer,bioinformatics
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