Prognostic value of comprehensive typing based on m6A and gene cluster

Abstract

Background Triple-negative breast cancer (TNBC) is resistant to targeted therapy with HER2 monoclonal antibodies and endocrine therapy because it lacks the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC is a subtype of breast cancer with the worst prognosis and the highest mortality rate compared to other subtypes. N6-methyladenosine (m6A) modification is significant in cancer and metastasis because it can alter gene expression and function at numerous levels, such as RNA splicing, stability, translocation, and translation. There has been limited investigation into the connection between TNBC and m6A. Materials and Methods Breast cancer-related data were retrieved from the Cancer Genome Atlas (TCGA) database, and 116 triple-negative breast cancer cases were identified from the data. The GSE31519 dataset, which included 68 cases of TNBC, was obtained from the Gene Expression Omnibus (GEO) database. Survival analysis was used to determine the prognosis of distinct m6A types based on their m6A group, gene group, and m6A score. To investigate the potential mechanism, GO and KEGG analyses were performed on the differentially expressed genes. Results The expression of m6A-related genes and their impact on prognosis in TNBC patients were studied. According to the findings, m6A was crucial in determining the prognosis of TNBC patients, and the major m6A-linked genes in this process were YTHDF2, RBM15B, IGFBP3, and WTAP. By cluster analysis, the gene cluster and the m6A cluster were beneficial in predicting the prognosis of TNBC patients. The m6A score based on m6A and gene clusters was more effective in predicting the prognosis of TNBC patients. Furthermore, the tumor microenvironment may play an important role in the process of m6A, influencing TNBC prognosis. Conclusion N6-adenylic acid methylation (m6A) was important in altering the prognosis of TNBC patients, and the key m6A-associated genes in this process were YTHDF2, RBM15B, IGFBP3, and WTAP. Furthermore, the comprehensive typing based on m6A and gene clusters was useful in predicting TNBC patients' prognosis, showing potential as a meaningful evaluating tools for TNBC.