Methylation Pattern Mediated by m⁶A Regulator and Tumor Microenvironment Invasion in Lung Adenocarcinoma

Recent research has established the existence of epigenetic modulation of the immune response. The possible involvement of RNA-n6-methyladenosine (m⁶A) alteration in tumor microenvironment (TME) cell invasion, on the other hand, is unknown.

Based on 23 m⁶A regulators, we examined the alteration patterns of m⁶A in 629 LUAD tissues and comprehensively connected these modification patterns with TME cell invasion characteristics. The m⁶A score was calculated, and the m⁶A modification pattern of a single tumor was quantified using principal component analysis. Then, we further verified the expression of m⁶A related enzymes and the role hub gene (NOL10) closely related to survival in lung cancer cell lines.

Three separate m⁶A alteration modes have been discovered. TME cell invasion characteristics in the three modes were very similar to the three immunological phenotypes of tumors: immunological rejection, immunological inflammation, and immunological desert. We show that assessing the m⁶A modification pattern in a single tumor may help predict tumor inflammatory stage, subtype, TME interstitial activity, and prognosis. TME phenotypic inflammation is indicated by a high m⁶A score, which is characterized by elevated mutation load and immunological activation. The low m⁶A subtype showed matrix activation and ineffective immune infiltration, indicating that the TME phenotype of noninflammation and immunological rejection had a poor survival probability. Increased neoantigen burden was also linked to a high m⁶A score. Patients with a higher m⁶A score saw substantial therapeutic and clinical improvements. And reducing hub gene NOL10 expression substantially inhibited lung cancer cell growth and migration.

This research shows that m⁶A alteration is critical in the creation of TME variety and complexity. The analysis of a single tumor's m⁶A alteration pattern will aid in improving our knowledge of TME invasion features and guiding more effective immunotherapy tactics.