Accuracy of early detection of colorectal tumours using stool methylation markers: A meta-analysis

doi:10.13105/wjma.v1.i3.147

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 1, Issue 3

This Article

Academic Content and Language Evaluation of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (4351)

All Articles published online

The chart showing PDF series, HTML series, Figures (1-4) series, Tables (1-4) series.

Item

Count

PDF

248

HTML

1740

Figures (1-4)

247

Tables (1-4)

255

Sum=2490

Publishing Process of This Article

The chart showing Browse series, Download series.

Item

Count

Browse

1079

Download

782

Sum=1861

Nov 26, 2013 (publication date) through Nov 4, 2024

Times Cited of This Article

Times Cited (0)

Journal Information of This Article

Publication Name

World Journal of Meta-Analysis

ISSN

2308-3840

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Meta-Analysis

World J Meta-Anal. Nov 26, 2013; 1(3): 147-156
Published online Nov 26, 2013. doi: 10.13105/wjma.v1.i3.147

Table 1 The characteristics of the included studies in the meta-analysis and QUADAS scores

Ref.	Country/region	Methylated genes	N	CRC		Adenoma		Normal		Blinddesign	Detection method	QUADAS score
Ref.	Country/region	Methylated genes	N	+	-	+	-	+	-	Blinddesign	Detection method	QUADAS score
Ahlquist et al[10]	Ireland	Vimentin/NDRG4/BMP3/TFPI2	98	26	4	18	4	5	41	Yes	QuARTS	11
Bosch et al[11], 2011	Netherlands	PHACTR3	185	40	25	6	13	4	97	Unclear	qMSP	10
		GATA4	160	29	11	3	16	6	95
		OSMR	185	25	40	4	15	7	94
Ahlquist et al[12]	Ireland	PHACTR3	639	214	38	51	43	29	264	Yes	QuARTS	11
Azuara et al[13]	Spain	RARB2/P16/MGMT/APC	98	25	13	20	20	0	20	Yes	MS-MCA	10
		RARB2	85	11	23	7	31	0	13
		P16	77	9	21	6	28	0	13
		MGMT	80	9	19	3	34	0	15
		APC	77	9	19	9	25	0	15
Tang et al[14]	China	SRRP2	262	142	27	29	34	2	28	Yes	MSP	9
Baek et al[15]	South Korea	Vimentin/MGMT/MLH1	149	45	15	31	21	5	32	Yes	MSP	9
		MLH1	149	18	42	6	46	0	37
		Vimentin	149	23	37	8	44	0	37
		MGMT	149	31	29	19	33	5	32
Li et al[16], 2009	United States	Vimentin	80	9	13	9	11	2	36	Unclear	Methl-BEAMing	5
Melotte et al[17], 2009	Netherlands	NDRG4	150	42	33	nr	nr	3	72	Yes	qMSP	11
Ausch et al[18], 2009	United States	IGTA4	37	nr	nr	7	2	6	22	Unclear	qMSP	4
Hellebrekers et al[19], 2009	Netherlands	GATA4	150	44	31	nr	nr	9	66	Yes	qMSP	10
Mayor et al[20], 2009	Spain	EN1	60	8	22	nr	nr	1	29	Unclear	MS-MCA	7
Kim et al[21], 2009	United States	OSMR/SFRP1	42	12	8	6	11	0	5	Yes	qMSP	9
		OSMR	201	35	54	2	14	4	92
		SFRP1	52	11	9	5	12	0	15
Nagasaka et al[22], 2009	Japan	SFRP2	253	53	31	18	38	9	104	Unclear	COBRA	10
Nagasaka et al[22], 2009	Japan	RASSF2	253	38	46	7	49	6	107	Unclear	COBRA	10
Glöckner et al[23], 2009	United States	TFPI2	129	44	14	7	19	2	43	Yes	qMSP	12
Wang et al[24], 2008	China	SFRP2	133	60	9	21	13	2	28	Yes	MethyLight	8
Oberwalder et al[25], 2008	Australia	SFRP2	19	nr	nr	6	7	0	6	Yes	MethyLight	9
Itzkowitz et al[26], 2008	United States	Vimentin	80	9	13	9	11	2	36	Yes	MSP	13
Huang et al[27], 2007	China	SFRP2/HPP1/MGMT	97	50	2	15	6	1	23	Yes	MSP	8
		SFRP2	97	49	3	11	10	1	23
		HPP1	97	37	15	12	9	0	24
		MGMT	97	25	27	6	15	0	24
Itzkowitz et al[28], 2007	United States	Vimentin/HLTF	162	31	9	nr	nr	19	103	Yes	MSP	13
		HLTF	162	15	25	nr	nr	9	113
		Vimentin	162	29	11	nr	nr	16	106
Abbaszadegan et al[29], 2007	Hong Kong	p16	45	5	20	nr	nr	0	20	Unclear	MSP	8
Zhang et al[30], 2007	Germany	SFRP1	44	16	4	7	0	2	15	Yes	MSP	9
Leung et al[31], 2007	Hong Kong	SFRP2/MGMT/MLH1/HLTF/ATM/APC	75	16	4	18	7	3	27	Yes	MSP	13
		SFRP2	75	6	14	3	22	2	28
		MGMT	75	4	16	3	22	0	30
		MLH1	75	4	16	3	22	0	30
		HLTF	75	5	15	5	20	1	29
		ATM	75	5	15	5	20	0	30
		APC	75	4	16	4	21	0	30
Petko et al[32], 2005	United States	MGMT/ CDKN2A/ MLH1	48	nr	nr	16	13	7	12	Yes	MSP	9
		CDKN2A	48	nr	nr	9	20	3	16
		MGMT	48	nr	nr	14	15	5	14
		MLH1	48	nr	nr	0	29	2	17
Lenhard et al[33], 2005	Germany	HIC1	71	11	15	4	9	0	32	Yes	MSP	11
Chen et al[34], 2005	United States	Vimentin	263	43	51	6	44	8	111	Yes	MSP	11
Müller et al[35], 2004	Australia	SFRP2/ SRRP5	39	20	3	nr	nr	8	8	Unclear	MethyLight	5
		SRRP2	39	19	4	nr	nr	4	12
		SRRP5	39	18	5	nr	nr	5	11
Xu et al[36], 2012	China	SFRP2	90	20	10	15	15	1	29	Unclear	MSP	5
Kang et al[37], 2011	China	MGMT/ MAL/ CDKN2A	119	64	5	17	7	2	24	Unclear	MSP	7
		MAL	119	54	15	14	10	1	25
		CDKN2A	119	36	33	10	14	0	26
		MGMT	119	38	31	9	15	1	25
Zhang et al[38], 2011	China	Vimentin/ OSMR/ TFPI2	107	52	8	13	4	4	26	Unclear	MSP	9
		Vimentin	107	32	28	5	12	0	30
		OSMR	107	41	19	7	10	0	30
		TFPI2	107	45	15	11	6	4	26
Fu et al[39], 2010	China	Vimentin	22	5	9	nr	nr	0	8	Unclear	MSP	5
Ling et al[40], 2009	China	P16	108	47	14	16	11	1	19	Unclear	MSP	7
Cheng et al[41], 2007	China	SFRP2	97	49	3	11	10	1	23	Unclear	MSP	5
Zhao et al[42], 2009	China	NDRG4	114	64	20	nr	nr	3	27	Unclear	MSP	6
Chang et al[43], 2010	South Korea	IGTA4/SFRP2/P16	86	21	9	18	7	1	30	Yes	MSP	8
		IGTA4	86	11	19	4	21	0	31
		SFRP2	86	18	12	11	14	0	31
		P16	86	12	18	6	19	1	30

+: Represents the number of individuals with the disease when the DNA methylation test was positive; -: Represents the number of individuals with the disease when the DNA methylation test was negative; nr: Not reported; N: Total number. CRC: Colorectal cancer.

Table 2 Methylation of pooled genes for the diagnosis of colorectal cancer

Wnt pathway	DNA damage repair pathway	Other pathways	SE (95%CI)	SP (95%CI)	DOR (95%CI)	AUC
Wnt pathway	DNA damage repair pathway	Other pathways	73% (0.71-0.75)	92% (90%-93%)	30.86 (22.33-42.66)	0.929
Wnt pathway	-	-	74% (70%-77%)	93% (90%-95%)	33.92 (17.73-64.90)	0.932
-	DNA damage repair pathway	-	42% (36%-47%)	97% (94%-99%)	12.87 (5.98-27.72)	0.730
-	-	Other pathways	57% (55%-60%)	94% (93%-95%)	20.93 (15.56-28.15)	0.921
SFRP2	-	-	79% (75%-82%)	93% (90%-96%)	47.57 (20.08-112.72)	0.957
-	MGMT	-	47% (40%-53%)	95% (90%-98%)	11.67 (5.10-26.67)	0.709
-	MLH	-	28% (18%-39%)	100% (95%-100%)	23.68 (3.02-185.44)	0.500
-	-	Vimentin	48% (42%-54%)	93% (90%-95%)	14.95 (8.99-24.84)	0.862
-	-	OSMR	47% (40%-54%)	95% (91%-98%)	14.66 (5.06-42.47)	0.225
-	-	P16	50% (42%-58%)	98% (92%-100%)	24.39 (7.26-81.96)	0.975
SFRP2	MGMT	-	69% (66%-72%)	94% (91%-96%)	33.24 (16.76-65.93)	0.946
SFRP2	MLH	-	72% (68%-75%)	94% (92%-96%)	43.03 (20.15-91.87)	0.953
SFRP2	MLH	Vimentin	64% (61%-67%)	94% (92%-95%)	27.11 (16.48-44.61)	0.934
SFRP2	MLH	OSMR	65% (62%-69%)	95% (93%-96%)	33.10 (17.12-63.98)	0.951
SFRP2	MLH	P16	68% (64%-71%)	95% (93%-97%)	38.86 (20.11-67.54)	0.952

SE: Sensitivity; SP: Specificity; DOR: Diagnostic odds ratio; AUC: The area under the curve.

Table 3 Methylation of pooled genes for the diagnosis of colorectal adenomas

Wnt pathway	DNA damage repair pathway	Other pathways	SE (95%CI)	SP (95%CI)	DOR (95%CI)	AUC
Wnt pathway	DNA damage repair pathway	Other pathways	51% (47%-54%)	92% (90%-93%)	12.61 (8.66-18.37)	0.883
Wnt pathway	-	-	40% (35%-46%)	95% (92%-97%)	10.81 (6.43-18.16)	0.932
-	DNA damage repair pathway	-	21% (17%-27%)	95% (91%-97%)	4.23 (2.01-8.88)	0.672
-	-	Other pathways	32% (28%-35%)	94% (93%-95%)	7.78 (5.48-11.05)	0.873
SFRP2	-	-	43% (38%-49%)	94% (91%-97%)	11.06 (5.77-21.18)	0.956
-	MGMT	-	29% (22%-36%)	93% (87%-96%)	4.42 (2.18-8.95)	0.614
-	MLH	-	8% (4%-16%)	98% (92%-100%)	2.35 (0.14-40.83)	-
-	-	Vimentin	23% (17%-31%)	95% (92%-98%)	8.30 (2.60-26.55)	0.898
-	-	OSMR	25% (14%-39%)	95% (91%-98%)	5.20 (1.44-18.82)	0.817
-	-	P16	33% (23%-44%)	97% (89%-100%)	13.27 (3.40-51.83)	0.97
SFRP2	MLH	-	34% (29%-39%)	95% (92%-97%)	9.62 (4.64-19.93)	0.947
SFRP2	MGMT	-	38% (33%-42%)	94% (91%-96%)	7.85 (4.79-12.87)	0.753
SFRP2	-	OSMR	41% (35%-46%)	95% (92%-96%)	9.25 (5.13-16.69)	0.948
SFRP2	-	Vimentin	36% (32%-41%)	95% (93%-96%)	9.88 (5.55-17.57)	0.946
SFRP2	-	P16	41% (36%-46%)	95% (92%-97%)	10.37 (6.21-17.31)	0.948
SFRP2	MGMT	Vimentin	34% (30%-38%)	94% (92%-96%)	7.81 (4.96-12.29)	0.804
SFRP2	MGMT	OSMR	36% (32%-41%)	94% (92%-96%)	7.25 (4.61-11.39)	0.775
SFRP2	MGMT	P16	37% (33%-41%)	94% (92%-96%)	7.92 (5.14-12.21)	0.772
SFRP2	MLH	Vimentin	31% (27%-35%)	95% (93%-97%)	8.99 (4.95-16.31)	0.944
SFRP2	MLH	OSMR	33% (29%-38%)	95% (93%-97%)	8.37 (4.50-15.59)	0.941
SFRP2	MLH	P16	34% (30%-38%)	95% (93%-97%)	9.98 (5.45-18.27)	0.947

SE: Sensitivity; SP: Specificity; DOR: Diagnostic odds ratio; AUC: The area under the curve.

Table 4 Weighted meta-regression on the diagnostic accuracy of the gene methylation assays

Covariate	Coefficient	SE	P value	RDOR	95%CI
QUADAS score¹	-0.259	0.419	0.541	0.77	(0.33, 1.82)
Detection method²	0.101	0.377	0.790	1.11	(0.51, 2.40)
Blinded design³	-0.179	0.381	0.642	0.84	(0.38, 1.82)
Methylated genes⁴	0.302	0.394	0.449	1.35	(0.60, 3.03)

¹Based on QUADAS score, studies were divided into those with higher quality (QUADAS score ≥ 10) and those with lower quality (QUADAS score < 10);

²Detection method, which was divided into qualitative and quantitative assay methods;

³Blinded design: the study was included with or without blinded design;

⁴Methylated genes, which were divided into single gene and combination genes. QUADAS: Quality Assessment for Studies of Diagnostic Accuracy was used to assess the quality of primary studies of diagnostic accuracy; SE: Standard error; RDOR: Relative diagnostic odds ratio.

Citation: Zhang H, Zhu YQ, Qi J, Wang QX, Cai SS, Zhu SY, Zhu XW, Wang XT. Accuracy of early detection of colorectal tumours using stool methylation markers: A meta-analysis. World J Meta-Anal 2013; 1(3): 147-156
URL: https://www.wjgnet.com/2308-3840/full/v1/i3/147.htm
DOI: https://dx.doi.org/10.13105/wjma.v1.i3.147