Abnormal DNA methylation as a cell-free circulating DNA biomarker for colorectal cancer detection: A review of literature

Table 1 DNA integrity index in colorectal cancer patients

Ref.	Increased DNA integrity	Decreased DNA integrity
Umetani et al[45], 2006	Yes	-
Da Silva Filho et al[46], 2013	Yes	-
Leszinski et al[47], 2014	Yes	-
Mouliere et al[48], 2011	-	Yes
Mead et al[49], 2011	-	Yes
Mouliere et al[50], 2014	-	Yes
Yörüker et al[51], 2015	-	Yes

Table 2 Abnormally methylated genes as potential circDNA blood-based colorectal cancer detection biomarkers

Potential biomarkers	CRC sensitivity (%)	CRC specificity (%)	Ref.
ALX4	40-83	70-82	[67,76]
TFPI2	76-89	-	[77-80]
SDC2	92	-	[81]
RUNX3	65	100	[82,83]
NEUROG1	52-64	91	[84]
MGMT	39	96	[74]
RARβ2	24	100	[74]
NGFR	51	84	[85]
9-Sep	48-90	86-93	[64-67,70,86]
TMEFF2	65	69	[85]
Vimentin	59	93	[41]
RASSF2A	58	100	[74]
Wif-1	74	98	[74]
APC	6	100	[87]
hMLH1	43	98	[87]
HTLF	21-34	98-100	[87,88]
SFRP2	67	94	[89]
CDKN2A/P16	71	100	[83]
Panel: SEPT9, HLTF and ALX4	74-88	90-96	[68]
Panel: SEPT9 and ALX4	-	-	[67]
Panel: MGMT, RASSF2A, Wif-1 gene	86.5	-	[74]
Panel: BMP3, NDRG4, vimentin, TFPI2, mutant KRAS and β-actin	87	-	[69]
Panel: AGTR1, WNT2, SLIT2	78	-	[71]
Panel: CINP1, FBN1, INA, SNCA, MAL and SPG20	90-99	-	[73]
Panel: CYCD2, HIC1, PAX5, RASSF1A, RB1 and SRBC	84	68	[72]
Panel: THBD and C9orf50	71	80	[75]
RASSF1A, E-cadherin	-	-	[72,90]
CAHM	-	-	[91]
FRP2, TPEF/HPP1	-	-	[83,84,92]

ALX4: Aristaless-like homeobox 4; TFPI2: Tissue factor pathway inhibitor 2; SDC2: Syndecan 2; RUNX3: Runt-related transcription factor 3; NEUROG1: Neurogenin 1; MGMT: O-6-methylguanine-DNAmethyltransferase; RARβ2: Retinoic acid receptor β2; NGFR: Nerve growth factor receptor; SEPT9: Septin 9; TMEFF2: Transmembrane protein with EGF-like, and two follistatin-like domains 2; RASSF2A: Ras association domain family 2 (isoform A); Wif-1: Wnt inhibitory factor-1; APC: Adenomatosis polyposis coli; hMLH1: MutL homolog 1; HTLF: Helicase-like transcription factor; SFRP2: Secreted frizzled-related protein 2; CDKN2A/P16: Cyclin-dependent kinase inhibitor 2A; BMP3: Bone morphogenetic protein; NDRG4: N-myc downstream regulated family member 4; KRAS: Kirsten rat sarcoma 2 viral oncogene homolog; AGTR1: Tissue fac angiotensin II receptor type 1; WNT2: Wingless-type MMTV integration site family member 2; SLIT2: Slit homolog 2 (Drosophila); CINP1 FBN1: Fibrillin 1; SNCA: α-synuclein gene; SPG20: Spastic paraplegia-20; CYCD2: D-type cyclin gene; HIC1: Hypermethylated in cancer 1; RASSF1A: Ras association domain family 1 (isoform A); RB1: Retinoblastoma tumor suppressor; SRBC: Sheep red blood cells; THBD: Thrombomodulin; C9orf50: Chromosome 9 open reading frame 50; FRP2: Frizzled related protein 2; TPEF/HPP1: Transmembrane protein containing epidermal growth factor, follistatin domain/hyperplastic polyposis 1.