Table 4.

Selected developing molecular biomarkers for colorectal cancer screening

Types	Sample	Molecular biomarker(s)	AUC (95% CI)	Sensitivity, % (95% CI)	Specificity, % (95% CI)	Ref.
DNA methylation	Plasma	APC, MGMT, RASSF2A, WIF1	0.927	86.5 (81.7−90.8)	92.1 (88.2−95.0)	[81]
	Plasma	BCAT1, IKZF1	NA	66	94	[82]
	Serum	SDC2	NA	87	95.2	[83]
	Plasma cfDNA	LINE-1	0.81	65.8	90	[84]
	Faeces	NDRG4	T: 0.77	T: 61 (43−79)	T: 93 (90−97)	[85]
			V: NA	V: 53 (39−67)	V: 100 (86−100)
	Faeces	TFPI2	NA	76 (60−88)	93 (77−99)	[86]
Circulating tumour DNA	Serum cfDNA	ALU115	0.8458	69.23	99.09	[87]
	ALU247/115	0.8551	73.08	97.27
Circular RNA (circRNA)	Plasma	91H, PVT1, MEG3	0.877	82.76	78.57	[88]
Serum	LOC285194, RP11- 462C24.1, Nbla12061	0.79 (0.71−0.86)	68.33	86.89	[89]
	Whole-blood	NEAT1_v1	0.73 (0.60−0.83)	56.7	83.3	[90]
	Whole-blood	NEAT1_v2	0.85 (0.73−0.93)	86.6	83.3	[90]
PIWI-interacting RNA (piRNA)	Serum	piR-5937	T: 0.8060	71.8	72.5	[56]
		V: 0.7673	73.6	65.3
		piR-28876	T: 0.8065	75.3	70.0	[56]
			V: 0.7074	66.0	65.3
microRNA (miRNA)	Plasma	miR-92a	0.885	89	70	[91]
Serum	miR-210	0.82	74.6	73.5	[92]
	Plasma	miR-24	8.84 (0.79−0.89)	78.4	83.9	[93]
	Faeces	miR-221	0.73 (0.68−0.78)	62 (55−68)	74 (67−80)	[60]
	Faeces	miR-20a	0.73 (0.68−0.78)	55 (47−62)	82 (76−87)	[57]
	Faeces	miR-135b	0.79	78 (69−85)	68 (58−77)	[59]
	Faeces	miR-92a, miR-21, miR-135b, miR-145, miR-133a	0.849	81	80	[94]
	Saliva	miR-21	NA	97	91	[95]
Exosomal microRNA	Plasma	miR-27a	0.87 (0.77−0.96)	81.82	90.91	[96]
Plasma	miR-130a	0.82(0.73−0.90)	69.32	100
Tumour-derived circulating cell	Whole-blood	Circulating endothelial cell clusters	0.92 (0.84−1.00)	NA	NA	[54]
Gut microbes	Faeces	F. nucleatum, Parvimonas micra	0.84	NA	NA	[76]
	Faeces	F. nucleatum, Clostridium hathewayi, Lachnoclostridium sp., Bacteroides clarus, and FIT	NA	93.8	81.2	[80]

95% CI, 95% confidence interval; NA, not available; T, training; V, validation; cfDNA, cell-free DNA.