After further analysis by screening the hypermethylated or hypomethylated CpG sites within the promoter regions from the transcription start site (TSS) [24], we identified six genes, CLDN16 (hypomethylated), HPS4, LZTFL1, FARS2, SGMS2, ABHD2 and RNF144A (hypermethylated), that were potentially dysregulated and could be a novel DNA methylation signature in the classification of tumor grading (Fig. 1e). The gene discussed is CLDN16; the disease is neoplasm.