However, as the relationship between the expression of CBLN2 and TMEM220 and DNA methylation transcriptional silencing has not been previously reported in COAD, we conducted qPCR and MSP analysis in NCM460, SW480, and SW620 cells, and found a DNA methylation transcriptional silencing relationship for CBLN2 and TMEM220. Moreover, the low expression of CBLN2 and TMEM220 was associated with poor prognosis in COAD patients by immunohistochemistry. Here, CBLN2 is linked to colon adenocarcinoma.