Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer

Table 1 Examples of genetic biomarkers for colorectal cancer

Biomarkers		Ref.
Genetic biomarkers	Prognosis
Breakpoints of 17p11.2	Found in primary colonic tumours in CRC patients with liver metastasis	[22]
Loss of 18q	Poor prognosis	[23,24]
Loss of SMAD	Advanced stage disease (III), lymph node metastases, shorter overall survival	[26]
APC mutations	Poorer overall survival	[39]
KRAS mutations	Heterogeneous phenotype of CRC	[43,44,45]
BRAF mutations	Specific phenotype and metastasis	[61,62]
PIK3CA mutations	Poor prognosis and specific clinicopathological features	[64]
Loss of PTEN	High rate of distant metastasis	[68]
TP53 expression	Worse prognosis	[70,71]
Loss of NDST4	Adverse prognosis	[72]
Candidate biomarkers	Chemoresistance/Chemosensitivity
Loss of SMAD4	Poorer response to 5-FU	[28]
MSI	Resistance to 5-FU	[83]
KRAS, BRAF, PI3KCA, PTEN mutations	Resistance to anti-EGFR mAb	[46-52,74,75,79-81]

CRC: Colorectal cancer; mAb: Monoclonal antibodies; 5-FU: 5-fluorouracil.

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]

¹Suggested 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.