Correlation Of M6a Methylation With Immune Infiltrates And Poor Prognosis In Non-Small Cell Lung Cancer Via A Comprehensive Analysis Of Rna Expression Profiles

Background: Non-small cell lung cancer (NSCLC) is a common type of lung cancer with a poor prognosis. N6-methyladenosine (m6A) methylation, which is a reversible ribonucleic acid (RNA) modification, plays an important role in the occurrence and development of NSCLC. However, the potential effect of m6A methylation on immune infiltrates and prognosis remains unclear.Methods: In this study, a weighted gene co-expression network analysis was used to screen out messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) that were co-expressed with m6A regulators. Additionally, 2 molecular subtypes (Clusters 1 and 2) were determined via consensus clustering. Subsequently, a prognostic risk model was constructed using both co-expressed mRNAs and ncRNAs. Based on the risk scores calculated by the prognostic model, the patients were divided into the high-risk group or low-risk group. Finally, the altered patterns of the tumor immune microenvironments (TIMEs) between the 2 stratification methods were thoroughly investigated, and a gene set enrichment analysis was conducted to further examine the potential mechanism.Results: Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival (OS) compared to patients in Cluster 2. A further investigation based on the prognostic model revealed that the PD-L1 expression levels of patients in the high-risk group were significantly upregulated, and the immunoscores were lower than those in the low-risk group. The immune cells with a high infiltration in Cluster 1 showed a significant positive correlation with the risk score; those with low infiltration showed a significant negative correlation. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, the second Gap/Mitosis (G2/M) checkpoint, E2 transcription Factor (E2F) targets, glycolysis, deoxyribonucleic acid (DNA) repair, and unfolded protein response were significantly enriched in Cluster 1, the low-immunoscore group, and the high-risk group.Conclusions: This study revealed that m6A methylation is closely related to the poor prognosis of NSCLC patients via interference with the TIME, which suggests that m6A may play a role in optimizing individualized immunotherapy management and improving prognosis.