Tumor microenvironment characteristics and prognostic role of mA modification in lung squamous cell carcinoma.

Background: It has recently been determined that N6-methyladenosine (mA) RNA methylation regulators have prominent effects on several cancers. However, the potential role of mA modification in lung squamous cell carcinoma (LUSC) remains unclear.

Methods: We evaluated the modification pattern of mA and studied the biological function of mA regulators in LUSC. Then, we constructed the m6Ascore to predict the prognosis of LUSC and analyzed the relationship between the m6Ascore and tumor mutation burden, immune cell infiltration, and immunotherapy.

Result: In the unsupervised consensus cluster analysis, three different m6Aclusters were identified, which correspond to an immune activation state, a moderate immune activation state, and an immune tolerance state. Forty-two genes related to the mA phenotype were used to construct the m6Ascore; subsequently, multiple validations of the m6Ascore were carried out to determine the relationship between the score and immune cell infiltration and response to CTLA-4/PD-1 inhibitor treatment. Further analysis revealed that the m6Ascore could effectively predict the prognosis of LUSC and that the mA phenotype-related genes, and , might be potential biomarkers.

Conclusion: These findings highlight the potential role of mA modification in the prognosis, TME, and immunotherapy of LUSC and have profound implications for developing more effective personalized treatment strategies for LUSC.