Comprehensive analysis of m⁷G modification patterns based on potential m⁷G regulators and tumor microenvironment...

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 (m⁷G) modification in shaping and impacting the TME remains unclear. Methods: A comprehensive analysis was performed to explore the m⁷G modification patterns based on 24 potential m⁷G regulators in 817 lung adenocarcinoma (LUAD) patients, and the TME landscape in distinct m⁷G modification patterns were evaluated. The m⁷G score was established based on principal component analysis (PCA) to quantify m⁷G 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 m⁷G 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 m⁷Gscore could predict the TME infiltrating characteristics, tumor mutation burden (TMB), response to immunotherapy and chemotherapy, as well as prognosis of individual tumors. High m⁷Gscore was associated with increased component of immune cell infiltration, low TMB and survival advantage, while low m⁷Gscore was linked to decreased immune cell infiltration and increased TMB. Additionally, patients with lower m⁷Gscore demonstrated significant therapeutic advantages. Conclusion: This study demonstrated the regulatory mechanisms of m⁷G modification on TME formation and regulation of lung adenocarcinoma. Identification of individual tumor m⁷G modification patterns will contribute to the understanding of TME characterization and guiding more effective immunotherapy strategies.