Current state and future direction of screening tool for colorectal cancer

Table 2 Summary of the current and potential biomarkers for early diagnosis of colorectal cancer

Characteristics of the studies				Training set [test set] (if applicable)			Diagnostic performance (if applicable)
Ref.	Study type, country	Study group	Population (n)	Male (%)	Age (mean / SD)	Stage (0) / I/ II/ III/ IV/ (?)	Sample	Marker	Sn / Sp	AUC / P-value
Microsatellites loci
Piñol et al[119], 2005	Prospective, multicenter, nation-wide study/Spain	CRC	1222	59.8	70/11	161/510/337/214	Blood	Bethesda panel	81.8/98	N/A
Umar et al[71], 2004	Guidelines	N/A	N/A	N/A	N/A	N/A	Blood	Bethesda panel	81.8/98	N/A
Berg et al[120], 2009	Recommendations	N/A	N/A	N/A	N/A	N/A	Blood	Microsatellites instability (MSI)	55-90/90	N/A
Liang et al[67], 2013	Meta‐analysis/China	N/A	N/A	N/A	N/A	N/A	Blood	APC Polymorphisms	N/A	N/A
CRC-specific RNA markers
Wu et al[77], 2014	Case-control China	Normal	109	45.9	60.4/7.0	I + II/III + IV/(?) 24/76/4	Stool	MiRNA-135b	78 (CRC) 73(Advanced adenoma) 65(any adenoma) /68	0.79 (CRC) 0.71 (adenoma) / <0.0001
			Adenoma < 1cm	110	53.6
			Advanced adenoma	59	50.7
			CRC	104	57.7
			IBD	42	61.9
Kalimutho et al[78], 2011	Case-control, Italy	CRC	28	46	66	(5)/2/6/3/0/(NA:12)	Stool	miRNA-148	74/87	N/A
		HGD	12	67	62
		Cn	39	28	58
Koga et al[74], 2010	Case-control, Japan	CRC	206	67	63	23/46/133/4	Stool	PTGS2	74.1/74.1	N/A, <0.0001
		Cn	134	44	60
Methylation biomarkers
Luo et al[86], 2011	Meta‐Analysis/China	N/A	N/A	N/A	N/A	N/A	Stool	VIM	80/80	N/A
Guo et al[88], 2013	Case-control, China	CRC	75	61	58.5 (12.5)	12/30/30/3	Stool	FBNI	72/93.3	N/A, < 0.001
		Cn	30	67	58.4 (12.9)
Glockner et al[89], 2009	Case-control, United States	CRC	26 [47]	52 [45]	69.33 [71.1]	Stage I to III	Stool	TFP12	89/93	N/A
		Adenoma	[19]		[61.4]
		Cn	45 [30]	46 [54]	55 [52.3]
Oh et al[90], 2013	Case-control, South Korea	CRC	131	69	58.4	26/57/36/12	Blood	SDC2	87/95	0.927, < 0.0001
		Cn	125	64	51
Grützmann et al[121], 2008	Case-control, Germany	CRC	252[126]	57 [60]	61 [67]	63/83/59/29/(NA:19)	Blood	Septin 9	48/93	N/A
		Cn	102[183]	35 [41]	59 [56]	[22/37/54/11/(NA:3)]			[58/90]
Warren et al[91], 2011	Case-control, United States	CRC	50	54	62	I + II/III + IV	Blood/Stool	Septin 9	90/88	N/A
		Cn	94	45	58	38/12
Tóth et al[92], 2012	Case-control, Hungary	CRC	93	52	67.8 (9.8)	25/14/36/18	Stool	Septin9 (gFOBT)	100/100	N/A
		Cn	94	38	62.6 (9.9)

SD: Standard deviation; Sn: Sensitivity; Sp: Specificity; AUC: Area under the curve; CRC: Colorectal cancer; N/A: Not available; Cn: control; IBD: Inflammatory bowel disease; HGD: High grade dysplasia; VIM: Vimentin; TFP12: Tissue factor pathway inhibitor 2.