Biomarkers for detecting colorectal cancer non-invasively: DNA, RNA or proteins?

Table 2 Non-invasive DNA, messenger RNA and long non-coding RNA biomarkers used for colorectal cancer detection

Study setting	Sample type	Marker type	Biomarker(s)	Sensitivity (or its range)	Specificity (or its range)	Ref.
Screening	Stool	DNA mutation panel	3 K-ras mutations, 10 APC mutations, 8 p53 mutations, microsatellite instability marker BAT-26 and long DNA marker	51.60%	94.40%	[46]
Case-control	Stool	Panel including DNA mutation, DNA methylation, DNA amount and protein testing	K-ras mutation, methylation of Vimentin (VIM), BMP3, NDRG4 and TFPI2 genes, DNA measurement by β-actin assessment and HemoQuant test for haemoglobin	78.0%-85.0%	85.0%-90.0%	[47]
Screening	Stool	Panel including DNA mutation, DNA methylation, DNA amount and protein testing	K-ras mutation, BMP3 and NDRG4 promoter methylation, DNA measurement by β-actin assessment and test for haemoglobin (FIT)	92.30%	86.60%	[48]
Case-control	Stool	Methylated DNA	BMP3 gene	51.0%-84.0%	90.0%-100.0%	[49]
Case-control	Stool	Methylated DNA	CDKN2A gene	20.0%-40.0%	84.0%-100.0%	[49]
Case-control	Stool	Methylated DNA	ECAD gene	65.20%	88.00%	[49]
Case-control	Stool	Methylated DNA	FBN1 gene	72.00%	93.30%	[49]
Case-control	Stool	Methylated DNA	GATA 4/5 gene promoter	42.9%-71.0%	84.0%-95.0%	[49,50]
Case-control	Stool	Methylated DNA	HLTF gene	20.0%-37.5%	90.0%-92.6%	[49]
Case-control	Stool	Methylated DNA	HIC1 gene	42.30%	98.00%	[49]
Case-control	Stool	Methylated DNA	HPP1 gene	71.20%	57.10%	[49]
Case-control	Stool	Methylated DNA	ING1b gene	73.70%	95.00%	[49]
Case-control	Stool	Methylated DNA	ITGA4 gene	40.00%	96.80%	[49]
Case-control	Stool	Methylated DNA	MGMT gene	33.9-55.1%	52.0%-100.0%	[49]
Case-control	Stool	Methylated DNA	NDRG4 gene promoter	53.0%-92.0%	89.1%-100.0%	[49-51]
Case-control	Stool	Methylated DNA	P16INK4A gene	71.70%	86.00%	[49]
Case-control	Stool	Methylated DNA	PHACTR3 gene	55.0%-66.0%	95.0%-100.0%	[49]
Case-control	Stool	Methylated DNA	RASSF2 gene	45.30%	94.70%	[49]
Case-control	Stool	Methylated DNA	SDC2 gene	81.10%	93.30%	[52]
Case-control	Stool	Methylated DNA	SEPT9 gene	20.0%-84.8%	80.0%-94.5%	[49]
Case-control	Stool	Methylated DNA	SFRP1 gene	26.4%-89.0%	86.0%-95.5%	[49]
Case-control	Stool	Methylated DNA	SFRP2 gene	32.1%-94.2%	54.0%-100.0%	[49,51]
Case-control	Stool	Methylated DNA	SPG20 gene	80.2%-89.0%	99.0%-100.0%	[49,51]
Case-control	Stool	Methylated DNA	SNCA gene	83.90%	75.00%	[49]
Case-control	Stool	Methylated DNA	TFPI2 gene	63.3%-92.0%	79.0%-100.0%	[49-51]
Case-control	Stool	Methylated DNA	TP53 gene	56.30%	100.00%	[49]
Case-control	Stool	Methylated DNA	Vimentin (VIM) gene	32.6%-86.0%	82.0%-100.0%	[49-51]
Case-control	Stool	Methylated DNA	WIF1 gene	19.3%-60.4%	96.7%-99.4%	[49]
Case-control	Stool	Methylated DNA	XAF1 gene	55.90%	52.00%	[49]
Case-control	Stool	Methylated DNA panel	BMP3 and NDRG4 genes	98.00%	90.00%	[49]
Case-control	Stool	Methylated DNA panel	MGMT and XAF1 genes	73.50%	52.00%	[49]
Case-control	Stool	Methylated DNA panel	MGMT-B and SFRP2 genes	88.30%	91.20%	[49]
Case-control	Stool	Methylated DNA panel	RASSF1A and SFRP2 genes	75.00%	89.40%	[51]
Case-control	Stool	Methylated DNA panel	SNCA and FNB1 genes	84.30%	93.30%	[53]
Case-control	Stool	Methylated DNA panel	Vimentin (VIM) and SFRP2 genes	92.50%	91.20%	[53]
Case-control	Stool	Methylated DNA panel	AGTR1, WNT2 and SLIT2 genes	74.0%-78.0%	88.0%-89.0%	[49,50]
Case-control	Stool	Methylated DNA panel	ECAD, MGMT and P16INK4A genes	72.00%	88.00%	[49]
Case-control	Stool	Methylated DNA panel	ITGA4, SFRP2 and P16INK4A genes	70.00%	96.80%	[49]
Case-control	Stool	Methylated DNA panel	MGMT, CDKN2A and hMTH1 genes	55.00%	63.00%	[49]
Case-control	Stool	Methylated DNA panel	MGMT, MLH1 and Vimentin (VIM) genes	75.00%	86.50%	[49,51]
Case-control	Stool	Methylated DNA panel	SFRP2, HPP1 and MGMT genes	93.70%	77.10%	[49]
Case-control	Stool	Methylated DNA panel	WIF-1, ALX-4 and Vimentin (VIM) genes	25.00%	98.00%	[49]
Case-control	Stool	Methylated DNA panel	Vimentin (VIM), OMSR and TFPI2 genes	86.70%	87.60%	[49]
Case-control	Stool	Methylated DNA panel	SFRP2, GATA4/5, NRDG4 and Vimentin (VIM) genes	96.40%	65.00%	[49]
Case-control	Stool	Human DNA content	Total human DNA content	66.00%	89.80%	[54]
Case-control	Bowel Lavage Fluid	Methylated DNA panel	miR-124-3, LOC386758 and SFRP1 genes	82.00%	79.00%	[55]
Case-control	Intrarectally collected colorectal mucus	Human DNA content	Total human DNA content	60.40%	94.80%	[56]
Case-control	Serum/plasma	Methylated DNA	ALX4 gene	23.0%-90.7%	72.5%-100.0%	[57]
Case-control	Serum/plasma	Methylated DNA	APC gene	57.0%-86.5%	86.0%-92.1%	[57]
Case-control	Plasma	Methylated DNA	CDH1 (E-cadherin) gene	60.00%	84.00%	[55]
Case-control	Serum/plasma	Methylated DNA	SDC2 gene	87.0%-90.7%	72.5%-95.2%	[36,57]
Case-control	Serum/plasma	Methylated DNA	SEPT9 gene	47.1-95.6%	81.0%-96.7%	[36,57-62]
Case-control	Serum/plasma	Methylated DNA	SFRP2 gene	54.0%-69.4%	40.0%-98.7%	[57,63]
Case-control	Plasma	Methylated DNA	THBD (Thrombomodulin) gene	70.70%	80.30%	[51]
Case-control	Serum/plasma	Methylated DNA	TPEF gene	65.0%-81.0%	69.0%-90.0%	[57]
Case-control	Serum/plasma	Methylated DNA	VIM (Vimentin) gene	59.0%-90.7%	72.5%-93.0%	[57]
Case-control	Plasma	Hypomethylated DNA	LINE-1 transposable DNA element	65.80%	90.00%	[36]
Case-control	Serum/plasma	Methylated DNA panel	IKFZ and BCAT1 genes	62.1%-95.0%	92.0%-95.0%	[36,57]
Case-control	Serum	Methylated DNA panel	SEPT9 and SDC2 genes	86.50%	92.10%	[64]
Case-control	Serum/plasma	Methylated DNA panel	APC, MGMT, RASSF2A and WIF-1 genes	86.50%	92.10%	[57]
Case-control	Plasma	Methylated DNA panel	ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9 and VIM genes	90.70%	72.50%	[63]
Case-control	Serum	ALU115 DNA content	Free ALU115 DNA content	69.20%	99.10%	[36]
Case-control	Serum	DNA integrity	ALU247/115 DNA integrity index	73.10%	97.30%	[36]
Case-control	Serum	Free DNA content	ALU-based cell-free DNA	64.50%	98.90%	[36]
Case-control	Whole blood	mRNA expression	TSPAN8 gene	83.60%	58.20%	[36]
Case-control	Whole blood	mRNA expression	LGALS gene	82.10%	61.20%	[36]
Case-control	Whole blood	mRNA expression	COL1A2 gene	73.10%	59.70%	[36]
Case-control	Whole blood	mRNA expression	CEACAM6 gene	65.70%	61.20%	[36]
Case-control	Whole blood or serum	mRNA expression	SALL4 gene	85.9%-96.1%	85.7%-95.0%	[65,66]
Case-control	Whole blood	mRNA expression panel	TSPAN8 and LGALS4 genes	92.50%	67.20%	[36]
Case-control (CRC and high-risk adenomas in the case group)	Whole blood	mRNA expression panel	LGALS4, CEACAM6, TSPAN8 and Col1A2 genes	75.00%	87.00%	[67]
Case-control	Whole blood	mRNA expression panel	CEA, EpCAM, CK19, MUC1, EGFR and C-Met genes	87.00%	85.00%	[68]
Case-control	Whole blood	Long non-coding RNA expression	NEAT1 variant 1	69.00%	79%	[36]
Case-control	Whole blood	Long non-coding RNA expression	NEAT1 variant 2	70.00%	96.00%	[36]
Case-control	Serum	Long non-coding RNA expression	BLACAT1	83.30%	76.70%	[69]
Case-control	Plasma	Long non-coding RNA expression panel	ATB and CCAT1	82.00%	75.00%	[70]
Case-control	Plasma	Long non-coding RNA expression panel	91H, PVT-1 and MEG3	82.80%	78.60%	[71]
Case-control	Serum	Long non-coding RNA expression panel	LOC285194, RP11-462C24.1 and Nbla12061	68.30%	86.90%	[72]

FIT: Faecal immunochemical test; CRC: Colorectal cancer.