Fig. 1

Analysis work flow. Adenocarcinoma and squamous cell carcinoma samples from Harvard, Spain, Norway, and Sweden cohorts were used for the discovery phase of analysis. Data from The Cancer Genome Atlas (TCGA) were used for validation. Ranger is a weighted version of random forest for controlling for the covariates including age, gender, smoking status, and histological stage. Variable importance score (VIS) was estimated for each CpG site and was ranked in descending order. CpG sites ranked in top 5% in both discovery and validation sets were selected for further evaluation by Cox regression. Multiple testing correction by false discovery rate (FDR) method was used if necessary