In the current study, DNA methylation profiling (Illumina Human Methylation 450K Bead Chip Array) and the following clinical data were downloaded from TCGA database. A total of 437 LUAD and 29 control specimens were enrolled in the methylation dataset, and clinical data included the survival time, status, gender, age, and clinical stage. To improve data accuracy, we preprocessed both of the two datasets. If the methylation level of a gene site is NA, which is more than 70% of the total samples, the locus is removed.21 (link) The clinical information of methylation data are shown in Table 1. The technical route to select the DNA methylated sites signature is shown in Fig. 1. We download the GSE56044 (n=97) dataset of GEO database for signature independent validation.