Table 2.
Examples of DNA methylation biomarkers for colorectal cancer diagnosis, progression, prognosis and treatment
| DNA methylation biomarkers | Ref. | |
| Methylated genes/loci | Frequently methylated in | |
| SLC5A8, SFRP1, SFRP2, CDH13, CRABP1, RUNX3, MINT1, MINT31, WNT5A | Normal colon epithelium → aberrant crypt focus | [11,105] |
| p14, HLTF, ITGA4, CDKN2A/p16, CDH1, ESR1 | Aberrant crypt focus → polyp/adenoma | [11] |
| TIMP3, CXCL12, ID4, IRF8, MGMT, hMLH1 | Polyp/adenoma → metastasis | [11] |
| SPARC, miR-34b/c, miR-126, miR-128 | Lymphovascular invasion, metastasis | [114-117] |
| Methylation biomarkers | CRC Diagnosis | |
| SEPT9, SFRP2, THDB, SBC2 | Blood-based PCR test for the detection of CRC | [91-97] |
| VIM, FBN1 | Stool-based test for the detection of CRC | [14,100] |
| Methylation biomarkers | Prognosis | |
| p14, RASSF1A, and APC | Poor prognosis | [107] |
| MGMT, hMLH1 | Improved survival | [107,108] |
| p16 | Poor prognosis | [109] |
| HOPX-β | Worse prognosis of stage III CRC | [110] |
| Extracellular matrix genes (IGFBP3, EVL, CD109 and FLNC) | Worse survival | [111] |
| IGF2 hypomethylation | Poor prognosis, short survival | [112] |
| Polycomb genes (SFRP1, MYOD1, HIC1, and SLIT2) | Favourable prognosis in non-CIMP male patients | [113] |
| miR-34b/c, miR-126, miR-128 | Invasive tumors | [115-117] |
| Candidate biomarkers | Chemoresistance/Chemosensitivity | |
| TFAP2E | No responsiveness to 5-FU, irinotecan, oxaliplatin | [118] |
| DYPD, TYMP, UMPK, SPARC | Their methylation might affect 5-FU treatment1 | [16,119] |
| UGT1A1 | Its methylation might affect irinotecan treatment1 | [119] |
| MGMT | Clinical response to dacarbazine is restricted to those with MGMT hypermethylation | [120] |
1
Suggested biomarkers from cell culture studies, with limited or no evidence in humans. CRC: Colorectal cancer; miR: micro-RNA; PCR: Polymerase chain reaction; 5-FU: 5-fluorouracil.