Department of Mammary Surgery I, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital,Yunnan Cancer Center), Kunming 650118, China.
Key Laboratory of the Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China.
Contrast Media Mol Imaging. 2022 May 21;2022:4416439. doi: 10.1155/2022/4416439. eCollection 2022.
Growing cutting-edge study has demonstrated the RNA m6A methylation's critical role in regulating tumorigenesis and progression all over the world, while it is still a mystery whether RNA m6A methylation has a positive impact on breast cancer treatment. In this article, we utilize bioinformatics to analyze three data sets including TCGA-BRCA, GSE96058, and GSE25066 and discover that breast cancer samples could be divided into 4 subtypes, which are quiescent, m6A methylation, protein-binding, and mixed, clarified by the expression level of m6A-related genes. R-survival analysis results also prove that the survival rate of breast cancer samples of the four subtypes significantly varies and remarkable differences in the number of exons' skip among the four subtypes can be seen according to the analysis of breast cancer gene expression characteristics. The degree of TP53 mutation and copy number loss is most obvious in the protein-binding subtype when it comes to tumor driver genes. Among the DNA damage repair genes, there is a sharp increase in the copy number of RAD54B of the protein-binding subtype, but fewer mutations in other DNA damage repair-related genes and copy number deletion is everywhere. Results of m6A methylation influencing on the proportion of infiltrated immune cells also indicate significant differences of the four m6A subgroups in macrophages M0 and mast cells resting which are closely correlated to patient prognosis. In addition, findings of the highest tumor stemness index and the lowest in the m6A methylated type in breast cancer samples can prove the critical role of the high expression of m6A reader protein in the progression of breast cancer.
日益增多的前沿研究表明,RNA m6A 甲基化在调节肿瘤发生和发展方面具有至关重要的作用,而 RNA m6A 甲基化是否对乳腺癌治疗有积极影响仍不清楚。在本文中,我们利用生物信息学方法分析了包括 TCGA-BRCA、GSE96058 和 GSE25066 在内的三个数据集,发现乳腺癌样本可以分为 4 种亚型,即静止型、m6A 甲基化型、蛋白结合型和混合型,这是由 m6A 相关基因的表达水平决定的。R 生存分析结果也证明了这一点,这四种亚型的乳腺癌样本的存活率存在显著差异,根据乳腺癌基因表达特征的分析,可以看到四种亚型之间外显子跳跃的数量存在显著差异。在肿瘤驱动基因方面,蛋白结合型的 TP53 突变和拷贝数丢失程度最为明显。在 DNA 损伤修复基因中,蛋白结合型 RAD54B 的拷贝数急剧增加,而其他与 DNA 损伤修复相关基因的突变较少,拷贝数缺失则随处可见。m6A 甲基化对浸润免疫细胞比例的影响结果也表明,四种 m6A 亚组在与患者预后密切相关的巨噬细胞 M0 和静止型肥大细胞中存在显著差异。此外,在乳腺癌样本中,m6A 甲基化型的肿瘤干细胞指数最高,而最低,这可以证明 m6A 阅读蛋白的高表达在乳腺癌的进展中起着关键作用。