Advances in epigenetic biomarker research in colorectal cancer

doi:10.3748/wjg.v20.i15.4276

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World Journal of Gastroenterology

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World J Gastroenterol. Apr 21, 2014; 20(15): 4276-4287
Published online Apr 21, 2014. doi: 10.3748/wjg.v20.i15.4276

Table 1 Biomarkers of DNA methylation in blood of colorectal cancer patients, n (%)

Markers	Sensitivity	Specificity	Ref.
APC	3 (6)	0 (100)	[20]
hMLH1	21 (43)	1 (98)	[20]
HLTF	17 (34)	1 (98)	[20]
HLTF	22 (21)	0 (100)	[21]
ALX4	25 (83)	9 (70)	[22]
TMEFF2	87 (65)	56 (69)	[23]
NGFR	68 (51)	29 (84)	[23]
9-Sep	92 (69)	25 (86)	[23]
9-Sep	90 (72)	19 (90)	[24]
9-Sep	24 (72)	3 (90)	[25]
9-Sep	18 (60)	5 (89)	[26]
9-Sep	45 (90)	11 (89)	[27]
NEUROG1	14 (52)-stage I 45 (64)-stage II	4 (91)	[28]
SFRP2	113 (67)	4 (94)	[29]
CDKN2A/P16	12 (71)	0 (100)	[30]
RUNX3	11 (65)	0 (100)	[30]
TPEF/HPP1	13 (13)	0 (100)	[21]

APC: Adenomatosis polyposis coli; hMLH1: Homo mutL homolog 1; HLTF: Helicase-like transcription factor; ALX4: ALX homeobox 4; TMEFF2: Transmembrane protein with EGF-like and two follistatin-like domains 2; NGFR: Nerve growth factor receptor; NEUROG1: Neurogenin 1; SFRP2: Secreted frizzled-related protein 2; CDKN2A: Cyclin-dependent kinase inhibitor 2A; RUNX3: Runt-related transcription factor 3; HPP1: Hyperpigmentation, progressive, 1; TPEF: Transmembrane protein endothalial factor.

Table 2 Biomarkers of DNA methylation in the stool of colorectal cancer patients

Markers	Sample	Sensitivity	Specificity	Ref.
AGTR1/WNT2/ SLIT2/VIM/SEPT9	214 CRC	20%-78%	86%-100%	[33]
	25 IBD
	39 controls
Vimentin/EYA4/ BMP3/NDRG4	CRC	67%-100%	89%	[34]
ESR1	19 CRC	65%	81%	[35]
ESR1	38 controls		81%	[35]
SLIT2	60 CRC		100%	[36]
	32 IBD associated CRC
	20 HR-IBD	25%
	65 LR-IBD
	28 controls
PHACTR3	64 CRC	66%	100%	[37]
	71 A	32%
	34 controls
TFPI2	60 CRC	68.3%	100%	[38]
	20 A
	30 controls
CNRIP1/FBN/INA/ MAL/SNCA/SPG20	78 CRC	65%-94%	95%-100%	[39]
	61 A	35%-91%
	48 controls
SPG20	9 CRC	67%	Unknown	[40]
MAL/CDKN2A/ MGMT	69 CRC	55.1%-78.3%	96.2%-100%	[41]
	24 A	37.5%-58.3%
	19 HP	10.5%-26.3%
	24 controls
3OST2	21 CRC	72.7%	90%	[42]
ITGA4/SFRP2/p16	30 CRC	70%	96.8%	[43]
	25 A	72%
	21 controls
RARB2/p16/ INK4a/MGMT/APC	26 CRC	62%	100%	[44]
	20 A	40%
	16 IBD	13%
	20 controls
RASSF1/SFRP2	84 CRC	75%	89%	[45]
	27 advanced A	44%
	29 non-advanced A	28%
	12 HP	25%
	4 IC	25%
	2 UC	100%
	113 controls
OSMR	69 CRC	38%	95%	[46]
OSMR	81 controls		95%	[46]
Vimentin	22 CRC	41%	95%	[47]
	20 advanced A	45%
	38 controls
MGMT/hMLH1/ Vimentin	60 CRC	75%	87%	[48]
	22 advanced A	46%
	30 non-advanced A	70%
	37 controls
ITGA4	13 A	69%	79%	[49]
NDRG4	75 CRC	53%-61%	93%-100%	[50]
NDRG4	75 controls		93%-100%	[50]
GATA4	75 CRC	51%-71%	84%-93%	[51]
GATA4	75 controls		84%-93%	[51]
TFPI2	26 CRC	76%-89%	79%-93%	[17]
TFPI2	45 controls		79%-93%	[17]
SFRP2	69 CRC	87.0%	93%	[52]
	34 A	61.8%
	26 HP	42.3%
	30 controls
SFRP2	13 A	46%	100%	[53]
	6 HP	33%
	6 controls
Vimentin	103 A	46%	84%	[54]
Vimentin	75 controls		84%	[54]
Vimentin/DIA	42 CRC	86%	73%	[55]
Vimentin/DIA	241 controls		73%	[55]
CDKN2A/p16/ MSI/long DNA	25 CRC	64%	95%	[56]
CDKN2A/p16/ MSI/long DNA	20 controls		95%	[56]
SFRP2	52 CRC	94%	93%	[57]
	10 advanced A	70%
	11:00 AM	36%
	8 HP	38%
	6 UC	17%
	24 controls
SFRP2/HPP1/ MGMT	52 CRC	96%	96%	[58]
	10 advanced A	80%
	11 non-advanced A	64%
	8 HP	38%
	6 UC	17%
	24 controls
Vimentin/DIA	40 CRC	88%	82%	[59]
Vimentin/DIA	122 controls		82%	[59]
ATM/APC/ MGMT/hMLH1/ HLTF/SFRP2/GSTP1	20 CRC	75%	90%	[60]
	30 A	68%
	30 controls
	241 controls
Vimentin	74 CRC	72%	89%	[61]
	62 A	84%
	70 controls
Vimentin	94 CRC	46%	90%	[62]
Vimentin	198 controls		90%	[62]
HIC1	26 CRC	42%	98%	[63]
	13 A	31%
	9 HP	0%
	41 controls
CDKN2A/MGMT/ hMLH1	29 A	55%	72%	[64]
	10 HP	40%
	25 controls
ATM/APC/ MGMT/hMLH1/ HLTF	20 CRC	70%	100%	[65]
ATM/APC/ MGMT/hMLH1/ HLTF	20 controls		100%	[65]
SFRP2	23 CRC	77%-90%	77%	[66]
	26 controls
	10 HP	40%
	25 controls

A: Adenoma; HP: Hyperplastic polyp; HR: High risk; LR: Low risk; IBD: Inflammatory bowel disease; IC: Ischemic colitis; UC: Ulcerative colitis; CRC: Colorectal cancer; AGTR1: Angiotensin II receptor, type 1; WNT2: Wingless-type MMTV integration site family member 2; SLIT2: Slit homolog 2; VIM: Vimentin; EYA4: Eyes absent homolog 4; BMP3: Bone morphogenetic protein 3; NDRG4: NDRG family member 4; ESR1: Estrogen receptor 1; PHACTR3: Phosphatase and actin regulator 3; TFPI2: Tissue factor pathway inhibitor 2; CNRIP1: Cannabinoid receptor interacting protein 1; FBN: Fibrillin; INA: Internexin neuronal intermediate filament protein, alpha; MAL: Mal, T-cell differentiation protein; SNCA: Synuclein, alpha; SPG20: Spastic paraplegia 20; MGMT: O-6-methylguanine-DNA methyltransferase; 3OST2: Heparan sulfate (glucosamine) 3-O-sulfotransferase 2; ITGA4: Integrin, alpha 4; RARB2: Retinoic acid receptor, beta 2; RASSF1: Ras association (RalGDS/AF-6) domain family member 1; OSMR: Oncostatin M receptor; GATA4: GATA binding protein 4; TFPI2: Tissue factor pathway inhibitor 2; CDKN2A: Cyclin-dependent kinase inhibitor 2; ADIA: DNA integrity assay; MSI: Microsatellite instability; GSTP1: Glutathione S-transferase pi 1; HIC1: Hypermethylated in cancer 1; ATM: Ataxia telangiectasia mutated; APC: Adenomatosis polyposis coli; hMLH1: Homo mutL homolog 1; HLTF: Helicase-like transcription factor; SFRP2: Secreted frizzled-related protein 2.

Table 3 MicroRNAs found in colorectal cancer but not in normal tissue

Up-regulated	miR-7, miR-17, miR-18a, miR-19a, miR-20a, miR-20, miR-21, miR-25, miR-29a, miR-29b, miR-32, miR-33a, miR-34a, miR-34b, miR-92a, miR-93, miR-95, miR-96, miR-101, miR-106a, miR-106b, miR-130, miR-135a, miR-135b, miR-181b, miR-182, miR-183, miR-191, miR-200c, miR-203, miR-222, miR-223, miR-224, miR-378, miR-155
Down-regulated	miR-30a, miR-30c, miR-34a, miR-125a, miR-126, miR-133a, miR-133b, miR-143, miR-145, miR-191, miR-192, miR-195, miR-215, miR-342, miR-497, miR-375, miR-378, miR-1, miR-9, miR-129, miR-137, miR-139

The underlined genes miR-34a, miR-191 and miR-378 were reported to be up-regulated in some studies[71-73] and down-regulated in others[74-76].

Table 4 MicroRNA biomarkers in the blood and stool of colorectal cancer patients

Markers	Sample	Sensitivity	Specificity	Ref.
Blood
miR-21	186 CRC	76.8%-82.8%	81.1%-90.6%	[77]
	43 A	91.9%	81.1%
	53 controls
miR-601/ miR-760	90 CRC	83.3%	69.1%	[78]
	48 AA	72.1%	62.1%
	58 controls
miR-21	30 CRC	90.0%	90.0%	[79]
miR-21	30 controls			[79]
miR-29a	258 plasma sample	75.0%	75.0%	[80]
miR-141	102 CRC	77.1%-90.9%	77.1%-89.7%	[81]
miR-92a	120 CRC	84.0%	71.2%	[82]
	37 AA	64.9%	81.4%
	59 controls
miR-29a	120 CRC	69.0%	89.1%	[82]
	37 AA	62.2%	84.70%
	59 controls
miR-221	103 CRC	86.0%	41.0%	[83]
miR-221	37 controls			[83]
miR-17-3P	90 CRC	64.0%	70.0%	[84]
miR-17-3P	50 controls			[84]
miR-92a	90 CRC	89.0%	70.0%	[84]
miR-92a	50 controls			[84]
Stool
miR-21	88 CRC	55.7%	73.3%	[85]
	57 polyps	43.9%
	101 controls
miR-92a	88 CRC	71.6%	73.3%	[85]
	57 polyps	56.1%
	101 controls
miR-144*	75 CRC	74.0%	87.0%	[86]
miR 17-92 cluster	197 CRC	69.5%	81.5%	[87]
miR 17-92 cluster	119 controls		81.5%	[87]
miR-135	197CRC	46.2%	95.0%	[87]
miR-135	119 controls		95.0%	[87]
miR-21	197 CRC	14.7%	91.6%	[87]
miR-21	119controls		91.6%	[87]
miR-92a	59 CRC	50.0%	80.0%	[88]
miR-92a	74 controls		80.0%	[88]
miR-21	59 CRC	50.0%	83.0%	[88]
miR-21	74 controls		83.0%	[88]

A: Adenoma; CRC: Colorectal cancer.

Table 5 Relationship between microRNAs and screening, diagnosis and prognosis in colorectal cancer

Screening	miR-17-92, miR-20a, miR-21, miR-92, miR-96, miR-106a, miR-135, miR-144, miR-203, miR-326, miR-181b, miR-601, miR-760
Diagnosis	miR-133b, miR-143, miR-145, miR-17-92, miR-18a, miR-20a, miR-21, miR-31, miR-92, miR-96, miR-135b, miR-183
Prognosis	miR-18a, miR-21, miR-20a, miR-31, miR-143, miR-145, miR-155, miR-181b, miR-200c, miR-203, miR-106a, miR-17-92, miR-135a, miR-335, miR-206, miR-10b, miR-146a/b, let7a/b
Treatment	miR-21, miR-17, miR-215, miR-125b, miR-137, miR-143, miR-145, miR-192, miR-622, miR-630

Citation: Wang X, Kuang YY, Hu XT. Advances in epigenetic biomarker research in colorectal cancer. World J Gastroenterol 2014; 20(15): 4276-4287
URL: https://www.wjgnet.com/1007-9327/full/v20/i15/4276.htm
DOI: https://dx.doi.org/10.3748/wjg.v20.i15.4276