“…Therefore, differences in DNAm patterns are expected and could potentially be exploited for better diagnosis and personalized treatments. Previous studies interrogating a list of selected genes suggest that methylation rates of ANK1 , APC , CCND2 , CDH13 , GATA3 , KCNH5 , LINE-1 , RARβ , RASSF1 , and RUNX3 are significantly higher in LUAD than in LUSC [ 13 , 17 , 136 , 137 , 138 ], while higher methylation frequencies of AGTR1 , CDKN2A/P16 , DAPK , HOXA9, MLH1 , SHOX2 , SFMTB2 , SFRP4 , TIMP3 , TGIF , and ZIC4 , are more often observed in LUSC compared to LUAD [ 13 , 94 , 98 , 102 , 139 , 140 , 141 , 142 ]. An early study using HumanMethylation27 BeadChips to examine 48 stage-I NSCLC tumors identified 263 hypermethylated CpG sites, and 513 hypomethylated CpG sites in LUSC compared to LUAD tumors [ 12 ].…”