Table 2 TP53 signaling pathway genes showing inverse relation between promoter DNA methylation and mRNA expression
Gene symbol | Gene name | promoter DNA methylation in our Metcap-Seq study* | mRNA expression in tumor/adenoma versus normal (logFCmin and logFCmax)** | Alterations in cancer/CRC/adenoma*** |
|---|---|---|---|---|
BAX | BCL2 associated X, apoptosis regulator | hypomethylated in adenoma | 0.36 and 1.09 | - downregulation in CRC [72] |
CDK1 | cyclin dependent kinase 1 | hypomethylated in adenoma | 0.42 and 2.12 | - overexpression in cancer [73] |
CDKN1A (p21) | cyclin dependent kinase inhibitor 1A | hypermethylated in CRC | −2.16 and − 0.67 | - loss of expression in CRC [74] |
CDKN2A (p16) | cyclin dependent kinase inhibitor 2A | hypermethylated in CRC hypermethylated in adenoma | −0.81 | |
CYCS | cytochrome c, somatic | hypermethylated in CRC hypermethylated in adenoma | −0.43 and − 1.83; − 0.33 and − 1.27 | - loss of protein expression in CRC and in adenoma [77] - its downregulation correlates with apoptosis resistance [77] |
DDB2 | damage specific DNA binding protein 2 | hypomethylated in adenoma | 1.31 and 1.54 | - suppresses tumorigenicity [78] - reduces invasiveness of CRC [79] - downregulated in high-grade CRC [79] |
GTSE1 | G2 and S phase expressed | hypomethylated in CRC hypomethylated in adenoma | 0.27 and 2.61 | |
IGFBP3 | insulin like growth factor binding protein 3 | hypermethylated in CRC hypermethylated in adenoma | −1.11 and − 2.27 | - hypermethylated in lung cancer [82] - downregulation in esophageal carcinoma [83] - lower level is associated with increased colon adenoma risk [84] |
SESN2 | sestrin 2 | hypermethylated in CRC | −1.86 and − 0.72 | - downregulation in tumors [85,86,87] - predicts unfavorable CRC outcome [85] |
SESN3 | sestrin 3 | hypomethylated in CRC | 0.46 and 1.09 | - involved in in vitro resistance to Irinotecan [88] |