AUTHOR=Ma Shouzheng , Zhu Jun , Wang Mengmeng , Zhu Jianfei , Wang Wenchen , Xiong Yanlu , Jiang Runmin , Liu Lei , Jiang Tao 

TITLE=Comprehensive analysis of m7G modification patterns based on potential m7G regulators and tumor microenvironment infiltration characterization in lung adenocarcinoma

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.996950

DOI=10.3389/fgene.2022.996950

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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<sup>7</sup>G) modification in shaping and impacting the TME remains unclear.</p><p><bold>Methods:</bold> A comprehensive analysis was performed to explore the m<sup>7</sup>G modification patterns based on 24 potential m<sup>7</sup>G regulators in 817 lung adenocarcinoma (LUAD) patients, and the TME landscape in distinct m<sup>7</sup>G modification patterns were evaluated. The m<sup>7</sup>G score was established based on principal component analysis (PCA) to quantify m<sup>7</sup>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.</p><p><bold>Results:</bold> We identified three distinct m<sup>7</sup>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<sup>7</sup>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<sup>7</sup>Gscore was associated with increased component of immune cell infiltration, low TMB and survival advantage, while low m<sup>7</sup>Gscore was linked to decreased immune cell infiltration and increased TMB. Additionally, patients with lower m<sup>7</sup>Gscore demonstrated significant therapeutic advantages.</p><p><bold>Conclusion:</bold> This study demonstrated the regulatory mechanisms of m<sup>7</sup>G modification on TME formation and regulation of lung adenocarcinoma. Identification of individual tumor m<sup>7</sup>G modification patterns will contribute to the understanding of TME characterization and guiding more effective immunotherapy strategies.</p>