PDF(Pubmed)
Abstract：
N6-methyladenosine (m6A) RNA methylation plays a pivotal role in immune responses and the onset and advancement of cancer. Nonetheless, the precise impact of m6A modification in lung adenocarcinoma (LUAD) and its associated tumor microenvironment (TME) remains to be fully elucidated. Here, we distinguished distinct m6A modification patterns within two separate LUAD cohorts using a set of 21 m6A regulators. The TME characteristics associated with these two patterns align with the immune-inflamed and immune-excluded phenotypes, respectively. We identified 2064 m6A-related genes, which were used as a basis to divide all LUAD samples into three distinct m6A gene clusters. We applied a scoring system to evaluate the m6A gene signature of the m6A modification pattern in individual patients. To authenticate the categorization significance of m6A modification patterns, we established a correlation between m6A score and TME infiltration profiling, tumor somatic mutations, and responses to immunotherapy. A high level of m6A modification may be associated with the aggressiveness and poor prognosis of LUAD. Further studies should investigate the mechanism of action of m6A regulators and m6A-related genes to improve the diagnosis and treatment of patients with LUAD.
摘要：
N6-甲基腺苷（m6A）RNA甲基化在免疫反应和癌症的发生和发展中起关键作用。尽管如此，m6A修饰对肺腺癌(LUAD)及其相关肿瘤微环境(TME)的确切影响仍有待完全阐明.这里,我们使用一组21个m6A调节剂在两个单独的LUAD队列中区分了不同的m6A修饰模式.与这两种模式相关的TME特征与免疫发炎和免疫排除表型一致。分别。我们确定了2064个m6A相关基因，以此为基础将所有LUAD样品分为三个不同的m6A基因簇。我们应用评分系统来评估个体患者中m6A修饰模式的m6A基因签名。为了验证m6A修改模式的分类意义，我们建立了M6A评分和TME浸润谱之间的相关性，肿瘤体细胞突变，以及对免疫疗法的反应。高水平的m6A修饰可能与LUAD的侵袭性和不良预后有关。应进一步研究m6A调节因子和m6A相关基因的作用机制，以提高LUAD患者的诊断和治疗水平。
