Diagnostic value of methylated branched chain amino acid transaminase 1/IKAROS family zinc finger 1 for colorectal cancer

Table 1 Information on the studies eligible for enrollment (%)

Ref.	Year	Country	Trial design	Disease	Detection method	Total volunteers	Cases (CRC)	Controls (non-CRC)	Sensitivity (95%CI)	Specificity (95%CI)	Sensitivity (95%CI)							Definition of a positive
											Stage I	Stage II			Stage III	Stage IV
Symonds et al[27]	2016	Australia	Prospective observational study	CRC screening	Real-time PCR	1381	66	1315	62 (49–74)	92 (90–93)	41 (18-67)	76 (55–91)			59 (33–82)	71 (29–96)		At least one PCR replicate was positive
Pedersen et al[32]	2015	Australia	Prospective observational study	CRC screening	Real-time PCR	218	74	144	77 (66-86)	92 (86-96)	50 (7-93)	68 (48-84)			87 (66-97)	100 (63-100)		A total change in fluorescence intensity above background levels was measured within 50 PCR amplification cycles
Winter et al[30]	2022	Australia	Prospective observational study	CRC screening	Real-time PCR	896	290	606	60 (54-66)	92 (89-94)	24 (14-37)		62 (51-72)	68 (58-77)			91 (78-97)	Methylation levels of 10% or more
Pedersen et al[32]	2015	Australia	Prospective observational study	CRC screening	Real-time PCR	967	129	838	66 (57-74)	94 (92-95)	38 (57-74)		69 (53-82)	73 (56-85)			94 (70-100)	At least one PCR replicate was positive
Saluja et al[35]	2021	Australia	Retrospective case–control study	CRC screening	Real-time PCR	1593	114	1479	61 (52-70)	91 (90-93)	NA		NA	NA			NA	At least one PCR replicate was positive
Young et al[28]	2016	Australia	Prospective observational study	Recurrent CRC detection	Real-time PCR	122	28	94	68 (48-84)	87 (79-93)	0/0		75 (35-97)	71 (44-90)			33 (1-91)	At least one PCR replicate was positive
Symonds et al[29]	2020	Australia	Prospective observational study	Recurrent CRC detection	Real-time PCR	144	50	94	66 (57-69)	98; (93 -100)	0/0		69 (39-91)	70 (51-85)			43 (10-82)	COLVERA (Clinical Genomics Pty, Ltd, North Ryde, New South Wales Australia) detectability of ctDNA
Pedersen et al[26]	2023	Australia	Prospective observational study	Recurrent CRC detection	Real-time PCR	142	33	109	27 (13-46)	91 (84-96)	NA		NA	NA			NA	0.07%
Pedersen et al[31]	2022	Australia	Prospective observational study	Recurrent CRC detection	Real-time PCR	549	77	472	64 (52-74)	98 (96-99)	NA		NA	NA			NA	0.07%
Musher et al[33]	2020	United States	Prospective observational study	Recurrent CRC detection	Real-time PCR	322	27	295	63 (42-81)	92 (88-94)	NA		NA	NA			NA	COLVERA (clinical Genomics Pathology Inc., NJ, United States) detectability of ctDNA
Symonds et al[34]	2022	Australia	Prospective observational study	Recurrent CRC detection	Real-time PCR	55	10	45	70 (35-93)	87 (73-95)	NA		NA	NA			NA	At least one PCR replicate was positive
Murray et al[36]	2018	Australia	Prospective observational study	recurrent CRC detection	real-time PCR	172	23	149	30 (13-53)	86 (79-91)	NA		NA	NA			NA	At least one PCR replicate

CRC: Colorectal cancer; CI: Confidence interval; PCR: Polymerase chain reaction; ctDNA: Circulating tumor DNA; NA: Not available.

Table 2 Subgroup analysis of the included studies based on the differences of the purpose of testing and the positive result definition (95% CI, %)

	Pooled sensitivity	Pooled specificity	Pooled positive likelihood ratio	Pooled negative likelihood ratio	Pooled diagnostic DOR	AUC
Overall	60 (53-67)	92 (90-94)	8.0 (5.8-11.0)	0.43 (0.36-0.52)	19 (11-30)	0.88 (0.85-0.91)
The purpose of testing
CRC screening	64 (59-69)	92 (91-93)	8.5 (7.1-10.1)	0.39 (0.33-0.45)	22 (16-30)	0.92 (0.89-0.94)
Assessment of recurrence	54 (42-67)	93 (88-96)	7.4 (3.9-14.2)	0.49 (0.37-0.66)	15 (6-37)	0.85 (0.81-0.88)
The definition of positive results
At least one PCR replicate	59 (50-67)	91 (89-93)	6.6 (4.6-9.5)	0.45 (0.36-0.56)	15 (8-26)	0.87 (0.84-0.90)
Set a specific threshold	61 (49-72)	94 (87-96)	10.5 (6.1-17.9)	0.42 (0.31-0.57)	25 (12-55)	0.91 (0.88-0.93)

AUC: Area under the curve; CRC: Colorectal cancer; CI: Confidence interval; PCR: Polymerase chain reaction.