Table 2.

DNA Methylation and miRNA-Based Biomarkers for Diagnosis, Prognosis, and Predictive Response to Chemotherapy in CRC

Marker	Purpose	Specimen type	Analysis method	Colorectal neoplasia	Remarks	Reference
DNA methylation
MLH1	Diagnosis	Serum	MSP	Hypermethylated	Diagnosis of sporadic MSI CRC	127
p16	Diagnosis	Serum	MSP	Hypermethylated	Diagnosis of CRC	128–130
DAPK	Diagnosis	Serum	MSP	Hypermethylated	Diagnosis of CRC	131
RUNX3	Diagnosis	Serum	MSP	Hypermethylated	Diagnosis of CRC	132
ALX4	Diagnosis	Serum	MS-AP-PCR	Hypermethylated	Diagnosis of colorectal adenomas and cancers	133
TMEFF2, NGFR, SEPT9	Diagnosis	Plasma	Microarray, qPCR	Hypermethylated	Diagnosis of CRC	134
Septin-9	Diagnosis	Plasma	MSP	Hypermethylated	Diagnosis of colorectal adenomas and cancers	135,136
APC, MGMT, RASSF2A, WIF1	Diagnosis	Plasma	MSP	Hypermethylated	Diagnosis of CRC	192
Vimentin	Diagnosis	Stool	MSP	Hypermethylated	Diagnosis of stage I and II CRCs	137
SFRP2, RASSF2	Diagnosis	Stool	COBRA, Hi-SA	Hypermethylated	Diagnosis of colorectal adenomas and cancers, and distinction from gastric cancer	138
NDRG4	Diagnosis	Stool	MSP	Hypermethylated	Diagnosis of CRC	140
GATA-5, GATA-5	Diagnosis	Stool	MSP	Hypermethylated	Diagnosis of CRC	139
BMP3, NDRG4, TFPI2, Vimentin	Diagnosis	Stool	QuARTS	Hypermethylated	Diagnosis of colorectal adenomas and cancers	141
Vimentin	Diagnosis	Stool, plasma	Methyl-BEAMing	Hypermethylated	Diagnosis of colorectal adenomas and cancers	193
BMP3	Diagnosis	Tissue	Bisulfite sequencing	Hypermethylated	Diagnosis of colorectal adenomas and cancers	194
HPP1, HLTF, MLH1	Prognosis	Serum	MSP	Hypermethylated	Hypermethylation of HLTF/HPP1 genes associated with unfavorable prognosis	195
LINE-1	Prognosis	Tissue	Pyrosequencing	Hypomethylation	Associated with worse OS	142
CIMP-high	Prognosis	Tissue	MSP	Hypermethylation	Associated with poor OS in advanced CRC	28
LINE-1	Predictive	Tissue	Pyrosequencing	Hypomethylation	Improved survival in patients treated with 5-FU–based adjuvant chemotherapy	142
CIMP-high	Predictive	Tissue	Pyrosequencing	Hypermethylation	Lack of benefit from 5-FU–based adjuvant chemotherapy in MSI CRCs	33
TFAP2E	Predictive	Tissue	MethyLight	Hypermethylation	Lack of responsiveness in patients with CRC treated with 5-FU–based chemotherapy	196
miRNAs
miR-92, miR-17-3p	Diagnosis	Plasma	qRT-PCR	Up-regulated	Diagnosis of CRC and distinction from other gastrointestinal cancers and inflammatory bowel disease	146
miR-92a, miR-29a	Diagnosis	Plasma	qRT-PCR	Up-regulated	Diagnosis of colorectal adenomas and cancers	147
miR-221	Diagnosis	Plasma	qRT-PCR	Up-regulated	Diagnosis of CRC and association with poor outcome	148
miR-21, miR-106a	Diagnosis	Stool	Mircoarray, qRT-PCR	Up-regulated	Diagnosis of colorectal adenomas and cancers	145
miR-135, miR-17-92 cluster	Diagnosis	Stool	qRT-PCR	Up-regulated	Diagnosis of CRC	149
miR-144	Diagnosis	Stool	qRT-PCR	Up-regulated	Diagnosis of CRC	150
miR-92a, miR-21	Diagnosis	Stool	qRT-PCR	Up-regulated	Diagnosis of colorectal adenomas and cancers	197
miR-21	Prognosis	Tissue	Microarray, qRT-PCR	Up-regulated	Associated with poor survival	90,152
miR-155	Prognosis	Tissue	qRT-PCR	Up-regulated	Associated with shorter DFS and OS	152
miR-320, miR-498	Prognosis	Tissue	Microarray	Up-regulated	Correlated with shorter recurrence-free survival	88
miR-185	Prognosis	Tissue	qRT-PCR	Up-regulated	Associated with shorter OS	198
miR-106a	Prognosis	Tissue	qRT-PCR	Down-regulated	Associated with shorter DFS and OS	199
miR-113b	Prognosis	Tissue	qRT-PCR	Down-regulated	Associated with shorter OS	198
miR-143	Prognosis	Tissue	qRT-PCR	Down-regulated	Associated with shorter OS	151
miR-141	Prognosis	Plasma	qRT-PCR	Up-regulated	Associated with poor survival
Let-7, miR-181b	Predictive	Tissue	qRT-PCR	Down-regulated	Associated with improved response to capecitabine-based chemotherapy	153
miR-21	Predictive	Tissue	Microarray, qRT-PCR	Up-regulated	Associated with poor response to 5-FU–based therapy	90,152
miR-125b, miR-137	Predictive	Tissue	qRT-PCR		Associated with worse response to capecitabine-based chemoradiotherapy	154

MSP, methylation-specific polymerase chain reaction; MS-AP-PCR, methylation-specific arbitrarily primer polymerase chain reaction; qPCR, quantitative polymerase chain reaction; QuARTS, quantitative allele-specific real-time target and signal amplification; OS, overall survival; qRT-PCR, quantitative reverse transcriptase polymerase chain reaction; DFS, disease-free survival.