Abstract
Background: The non-negligible role of epigenetic modifications in cancer development and tumor microenvironment (TME) has been demonstrated in recent studies. Nonetheless, the potential regulatory role of N7-methylguanosine (m(7)G) modification in shaping and impacting the TME remains unclear. Methods: A comprehensive analysis was performed to explore the m(7)G modification patterns based on 24 potential m(7)G regulators in 817 lung adenocarcinoma (LUAD) patients, and the TME landscape in distinct m(7)G modification patterns were evaluated. The m(7)G score was established based on principal component analysis (PCA) to quantify m(7)G modification patterns and evaluate the TME cell infiltrating characteristics of individual tumors. Further, correlation analyses of m7Gscore with response to chemotherapy and immunotherapy were performed. Results: We identified three distinct m(7)G modification patterns with the biological pathway enrichment and TME cell infiltrating characteristics corresponded to immune-desert, immune-inflamed and immune-excluded phenotype, respectively. We further demonstrated the m(7)Gscore could predict the TME infiltrating characteristics, tumor mutation burden (TMB), response to immunotherapy and chemotherapy, as well as prognosis of individual tumors. High m(7)Gscore was associated with increased component of immune cell infiltration, low TMB and survival advantage, while low m(7)Gscore was linked to decreased immune cell infiltration and increased TMB. Additionally, patients with lower m(7)Gscore demonstrated significant therapeutic advantages. Conclusion: This study demonstrated the regulatory mechanisms of m(7)G modification on TME formation and regulation of lung adenocarcinoma. Identification of individual tumor m(7)G modification patterns will contribute to the understanding of TME characterization and guiding more effective immunotherapy strategies.