Comprehensive analysis of m6A regulator signature for prediction of prognosis and immune cell infiltration in lung adenocarcinoma

Abstract

OBJECTIVE: This study aimed to elucidate the molecular mechanism of N6-methyladenosine (m6A)regulation in lung adenocarcinoma (LUAD) development.METHODS: Gene expression profiles were derived from the TCGA and GEO databases. Theexpression levels of m6A regulators in LUAD and normal tissues were assessed. Consensus clustering wasconducted for differential tumor subtypes. m6A regulators related to prognosis were screened using theLASSO algorithm. A score (RS) system was constructed and verified. The correlation between the riskscore signature, prognosis, and immune cell infiltration was further analysed.RESULTS: We identified the modification features of m6A regulators in LUAD and found that 16m6A genes were aberrantly expressed in tumor tissue compared with normal tissue. Six optimised m6Aregulators, including FTO, RBM15B, and RBMX, were obtained to construct a risk score system. Moreimportantly, the AUC values of the ROC curve were 0.790, 0.729, 0.776, and 0.765 for the four datasets,indicating high predictive ability. Patients in the high-risk group had worse prognoses than those in thelow-risk group (P <0.05). Three clinical factors (RS status, pathological stage, and tumor recurrence)correlated independently with survival outcomes. The proportions of the four immune cell types showedabnormal changes in the two risk groups. The m6A regulatory signature was significantly related toinfiltration by immune cells, such as B cells, CD4+ and CD8+ T cells, and neutrophils (P <0.05).CONCLUSION: We demonstrated the potential roles of six m6A regulators in LUAD progression andimmune cell infiltration. The risk score signature may serve as a reliable tool for prognosis prediction andmay provide effective guidance in LUAD therapy.