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and 87%, respectively. Kamimae et al. have recently associated with poor prognosis. However, all of these
[80]
[88]
shown that detection of DNA methylation in mucosal possible markers need to be further validated before they
wash fl uid from patients undergoing colonoscopy may be are used clinically.
a good molecular marker for predicting invasiveness of Global hypo-methylation may infl uence tumor progression
colorectal tumors. [81]
by making chromosomes more susceptible to breakage
Promoter hypermethylation of MLH1, MGMT and causing disruption of normal gene structure and
and HIC1 can be detrimental and lead to cancer function, leading to reactivating previously silenced
progression. [82-85] Seven additional genes (TIMP3, retrotransposons. [89-91] Most recent research on LINE-1
CXCL12, ID4, IRF8, CHFR, IGFBP3 and CD109) were methylation levels in GI cancers has focused on colorectal
frequently methylated in late-stage colorectal cancer and cancer; Ogino et al. reported LINE-1 methylation
could have a role in colorectal cancer progression and levels widely occurred and approximately normally
metastasis. [71,86,87] Yi et al. observed that colorectal cancers distributed (range: 23.1-90.3%) in a cohort of 869
[92]
that have silenced (methylated) genes in the extracellular colorectal cancer patients. LINE-1 hypo-methylation
matrix-remodeling pathway, such as IGFBP3, EVL, was inversely associated to the MSI and CIMP; [92,93]
CD109 and FLNC, showed worse survival, suggesting these fi ndings suggest that CIMP/MSI and genomic
that methylation of this pathway-related genes might hypo-methylation represent different pathways in
represent a prognostic signature for colorectal cancer colorectal cancer development. A summary of reported
patients. Moreover, hypo-methylation of the IGF2 gene methylation in stool, blood and tissue samples of
[87]
differentially methylated region in colorectal tumors was patients with colorectal cancer is shown in Tables 3 and 4.
Table 3: Association of gene promoter methylation with diagnosis of colorectal cancer
Gene Specimen type Correlation with clinical outcomes References
DNA hypermetylation Diagnosis
AGTR1 Stool Diagnosis of CRC [112]
ALX4 Blood Diagnosis of colorectal adenomas and cancers [113]
APC Blood Diagnosis of CRC [114]
BMP3 Stool Diagnosis of colorectal adenomas and cancers [115]
BMP3 Tissue Diagnosis of colorectal adenomas and cancers [112]
CNIP1 Stool Diagnosis of CRC [116]
DAPK Blood Diagnosis of CRC [117]
FBN1 Stool Diagnosis of CRC [116]
GATA-5 Stool Diagnosis of CRC [118]
IGFBP7 Cells Diagnosis of CRC [119]
INA Stool Diagnosis of CRC [116]
MAL Stool Diagnosis of CRC [116]
MGMT Blood Diagnosis of CRC [114]
MLH1 Blood, cells Diagnosis of sporadic MSI CRC [73]
NDRG4 Stool Diagnosis of CRC [120]
NDRG4 Stool Diagnosis of colorectal adenomas and cancers [115]
NEUROG1 Blood Diagnosis of CRC [121]
NGFR Blood Diagnosis of CRC [74]
p16 Blood Diagnosis of CRC [122]
RASSF2 Stool Diagnosis of CRC, distinction from gastric cancer [123]
RASSF2A Blood Diagnosis of CRC [114]
RUNX3 Blood Diagnosis of CRC [124]
SDC2 Blood Diagnosis of CRC [125]
SEPT9 Blood Diagnosis of CRC [74,75]
SFRP2 Stool, blood, tissue Diagnosis of CRC, distinction from gastric cancer [123]
SLIT2 Stool Diagnosis of CRC [112]
SNCA Stool Diagnosis of CRC [116]
SPG20 Stool Diagnosis of CRC [116]
TFPI2 Stool Diagnosis of colorectal adenomas and cancers [115]
TMEFF2 Blood Diagnosis of CRC [74]
Vimentin Stool, blood Diagnosis of colorectal adenomas and cancers [126]
WIF1 Blood Diagnosis of CRC [114]
WNT1 Stool Diagnosis of CRC [112]
CRC: Colorectal cancer; MSI: Microsatellite instability

Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 3 ¦ October 15, 2015 ¦ 117