Biomarkers in colorectal cancer: Current clinical utility and future perspectives

Table 1 Examples of biomarkers for colorectal cancer diagnosis, progression, prognosis and treatment

Biomarker		Prognostic factor	Predictive factor
BRAF mutations	Specific phenotype and metastasis; resistance to anti-EGFR mAb	Yes[6,110]	Yes[111], Potentially[6,110]
KRAS mutations	Heterogeneity of CRC; resistance to anti-EGFR mAb	Yes potentially[110]	Yes[6,110,111]
MSI	Resistance to 5-FU	Yes[6,110], No[111]	-
APC mutations	Poorer overall survival	Yes[66]	Yes[65]
Micro-RNA	Early detection of CRC, prognostic stratification and therapy-response prediction	Yes[72]	Yes[73]
PIK3CA mutations	Poor prognosis and particular clinico-pathological characteristics; resistance to anti-EGFR mAb	Yes[82]	Yes[110]
Loss of PTEN	High tendency to develop metastasis; Resistance to anti-EGFR mAb	-	Yes potentially[110,111]
TP53 expression	Poor prognosis	Yes potentially[110], No[111]	-
Loss of NDST4	Adverse prognosis; molecular predictor of metastasis	Yes[95]	Yes[95]
Loss of 18qLOH	Poor prognosis	Yes[111], Potentially[110]	-
IGFR-1R	High levels in metastastic CRC; poor overall survival	Yes[104]	Yes[104]

National Comprehensive Cancer Network Guidelines[6]; European Society for Medical Oncology Guidelines[110]; American Society of Clinical Oncology Guidelines[111]. CRC: Colorectal cancer; EGFR: Epidermal growth factor receptor; MSI: Microsatellite instability; FU: Fluorouracil.

Table 2 Examples of epigenetic biomarkers for colorectal cancer

Epigenetic markers
Methylated genes/loci
p14 ARF, p15 INK 4b, p16 INK4a	Cell cycle regulation
hMLH1, MGMT	DNA repair system; progression from adenoma to cancer
DAPK	Apoptosis
THBS1	Angiogenesis inhibition
SPARC	Lymphovascular invasion, metastasis
TIMP3	Metastasis suppression
CDH1, CDH13	Cell adherence
Methylation biomarkers
VIM, SEPT9, SFRP2	Biomarkers for CRC and as DNA-based colon cancer screening tests
TWIST1, IGFBP3, GAS7, ALX4, SDC2	Higher methylation levels in CRC compared to normal subjects (promising diagnostic biomarkers)
Candidate biomarkers
Methylated UGT1A1	Affects irinotecan treatment (in vitro)
Methylated DYPD, UMPK, and SPARC	Affect 5-FU treatment (in vitro)
TFAP2E	No responsiveness to oxaliplatin, irinotecan, and 5-FU

CRC: Colorectal cancer; FU: Fluorouracil.