Establishment of a 5 DNA Methylation Site Prognostic Signature Associated with N6-Methyladenosine in Lung Adenocarcinoma

Background: There is a high incidence of lung adenocarcinoma (LUAD). Even with surgery, targeted therapy and immunotherapy, the survival rate of LUAD patients is still low. N6-methyladenosine (m6A) and DNA methylation markers can help with the diagnosis and treatment of LUAD patients. Therefore, it is necessary to identify a novel m6A-related DNA methylation sites signature to predict the survival of patients with LUAD. Methods: In this study, we screened 15 m6A-related genes and their 217 methylation sites. RNA sequencing data of 15 genes and the clinicopathological parameters of TCGA-LUAD were obtained from the TCGA database (http://cancergenome.nih.gov/). The LUAD-DNA CpG site information was obtained from the Illumina Human Methylation 450 BeadChip (Illumina, San Diego, CA, United States). The methylation sites related to prognosis were screened using univariate COX analysis, and the independent predictors of LUAD patients were identified using multivariate COX analysis of least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Finally, a model with 5 methylation sites as the main body to predict the prognosis of OS in patients with LUAD was obtained. According to the risk grouping of the prediction model, Kaplan-Meier curve and the receiver operating characteristic (ROC) curve were performed in the test and training sets to assess the predicted capacity of the model. In addition, a nomogram constructed by combining the risk score of methylation group and other related clinicopathological factors to verify the reliability of our model.Results: We constructed a m6A-related 5-DNA methylation site model to predict OS in LUAD patients. According to the results of the Kaplan-Meier curve, both the test set and the training set, the high-risk group showed a worse prognosis. The AUCs of the 5 DNA methylation signature at 1, 5 and 10 years in test datasets were 0.730, 0.649 and 0.726, respectively, and 0.679, 0.656 and 0.732 in training datasets. Finally, we constructed a nomogram to further verify the reliability of the model.Conclusion: In this study, we analyzed the methylation sites of m6A-related genes and established a m6A-related 5-DNA methylation site model to predict OS in LUAD patients.