High levels of m6A methylation and histone acetylation modification patterns contribute to the survival of LUAD patients

Abstract: Background The m6A methylation-regulated histone acetylation modification affects the proliferation and differentiation of mouse embryonic neural stem cells, and recent studies have shown that the deacetylase SIRT1 regulates RNA m6A methylation to promote hepatocellular carcinogenesis. However, the interrelationship between the m6A methylation and histone acetylation, and the potential roles as well as interactions of related regulators in TME cell infiltration and drug sensitivity have not been explored at a holistic level. Methods Unsupervised clustering method was used to identify lung adenocarcinoma m6A modification patterns based on 14 m6A regulators and histone acetylation modification patterns based on 37 histone acetylation regulators. Individual samples were then quantified based on their differential gene construction models. Finally, the models were analysed in relation to transcriptional background and TME characteristics to predict potential target drugs and explore the association of m6A methylation with histone acetylation. Result Three histone acetylation patterns as well as two m6A methylation patterns were identified. Patients with LUAD in the low-score group had poorer overall survival times and more active cancer-related malignant pathways. m6A methylation was strongly associated with histone acetylation, and high levels of m6A methylation and histone acetylation patients had significantly superior survival and immunoreactivity. VX-680 and GW843682X may be potential drugs available for the low level m6A group. Conclusion This work revealed that m6A modifications and histone acetylation modifications have a non-negligible role in the development of TME diversity and complexity. We found that both m6A methylation and histone acetylation are closely associated with tumor malignant pathways. Combined m6A methylation and histone acetylation analysis will help to obtain the understanding of tumor internal regulation and provide new therapeutic directions.