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Table 3 Overall survival among patients with colorectal cancer according to CIMP status

From: Different definitions of CpG island methylator phenotype and outcomes of colorectal cancer: a systematic review

CIMP definition

First author (year)

Subgroup

Subgroup size

Analysis

Survival

HR (95 % CI)

Comparison group

p value

Covariates adjusted for

CIMP+/CIMP-H

CIMP-L

CRC patients

          

 D 1

Lee (2008) [16]

All

134

U

OS

1.59 (0.87–2.88)

 

CIMP−

0.13

No

 D 2

Sanchez (2009) [21]

All

391

M

OS

1.56 (0.88–2.78)a

 

CIMP−

0.13

Age, sex, stage, location, MSIb

 D 6

Ward (2003) [37]

All

609

U

OS

1.30 (0.70–2.20)

 

CIMP−

0.37

No

 D 7

Kakar (2012) [39]

All

33

U

OS

1.19 (0.51–2.58)

 

CIMP−

0.69

No

 D 14

Li (2014) [34]

All

282

M

OS

2.31 (1.02–5.24)

 

CIMP−

0.04

Age, stage, location, differentiation

 D 2

Samadder (2013) [30]

All

563

M

OS

1.12 (0.81–1.55)

0.86 (0.60–1.23)

CIMP-N

0.60

Age, stage, grade, locationc

 D 3

Kim (2009) [18]

All

320

U

OS

1.81 (0.91–3.66)

1.33 (0.78–2.27)

CIMP-N

0.24

No

 D 4

Kim (2009) [18]

All

320

U

OS

2.46 (1.16–5.19)

1.30 (0.76–2.22)

CIMP-N

0.05

No

 D 14

Li (2014) [34]

All

282

M

OS

3.06 (1.19–7.89)

0.95 (0.60–1.52)

CIMP-N

0.02

Age, stage, location, differentiation

CRC patients by cancer stages

 D 14

Li (2014) [34]

I–III

149

M

OS

0.52 (0.12–2.22)

 

CIMP−

0.38

Age, stage, location, differentiation

 D 6

Ward (2003) [37]

I–III

476

U

OS

1.20 (0.60–2.80)

 

CIMP−

0.60

No

 D 11

Barault (2008) [14]

I–II, colon, MSS

246

M

OSd

2.90 (1.53–5.49)

1.85 (1.37–2.51)

CIMP-N

<0.01

Age, stage, BRAF, KRAS

 D 2

Donada (2013) [40]

II, colon

120

M

OS

0.60

 

CIMP−

0.30

All variablese

 D 14

Li (2014) [34]

III–IV

129

M

OS

1.75 (0.95–3.23)

 

CIMP−

0.07

Age, stage, location, differentiation

CRC patients by location of CRC

 D 3

Bae (2013) [28]

Proximal

165

M

OS

0.84 (0.42–1.69)

 

CIMP−

0.62

Stage, differentiationf

 D 3

Bae (2013) [28]

Distal

327

M

OS

1.35 (0.47–3.90)

 

CIMP−

0.58

Stage, differentiationf

 D 4

Ogino (2009) [19]

Colon

649

M

OS

0.78 (0.47–1.29)

1.01 (0.77–1.33)

CIMP-N

 

Age, sex, stage, BRAF, KRAS, MSIg

 D 2

Donada (2013) [40]

Colon, II

120

M

OS

0.60

 

CIMP−

0.30

All variablese

 D 1

Samowitz (2005) [13]

Colon, MSS

803

M

OS

0.88 (0.66–1.18)

 

CIMP−

 

Age, stage, location, BRAF

 D 11

Barault (2008) [14]

Colon, MSS, I–II

246

M

OSd

2.90 (1.53–5.49)

1.85 (1.37–2.51)

CIMP−

<0.01

Age, stage, BRAF, KRAS

 D 3

Bae (2013) [28]

Rectal

242

M

OS

4.13 (1.27–13.46)

 

CIMP−

0.02

Stage, differentiationf

CRC patients by microsatellite instability

 D 1

Lee (2008) [16]

MSS

115

U

OS

1.96 (1.06–3.61)

 

CIMP−

0.03

No

 D 6

Ward (2003) [37]

MSS

547

M

OS

2.10 (1.10–4.00)

 

CIMP−

0.02

Stage, vascular space invasion

 D 7

Kakar (2008) [15]

MSS

69

M

OS

0.86 (0.35–2.13)

 

CIMP−

0.70

Age, sex, stage, LOH, BRAF

 D 6

Ward (2003) [37]

MSS, I–III

464

M

OS

2.40 (0.94–6.00)

 

CIMP−

0.06

Stage, vascular space invasion

 D 1

Samowitz (2005) [13]

MSS, colon

803

M

OS

0.88 (0.66–1.18)

 

CIMP−

 

Age, stage, location, BRAF

 D 11

Barault (2008) [14]

MSS, colon, I–II

246

M

OSd

2.90 (1.53–5.49)

1.85 (1.37–2.51)

CIMP-N

<0.01

Age, stage, BRAF, KRAS

CRC patients by microsatellite instability

 D 3

Bae (2011) [23]

MSI

169

M

OS

2.81 (1.08–7.27)

 

CIMP−

0.03

Age, stage, BRAF, differentiationh

 D 3

Rhee (2012) [26]

MSI

207

M

OS

3.05 (1.07–8.73)

 

CIMP−

0.04

Age, stage, location, BRAF/KRASi

  1. CI confidence interval, HR hazard ratio, M multivariate analysis, OS overall survival, U univariate analysis
  2. aThe original data of HR (95 % CI) was 0.64 (0.36–1.14) derived from CIMP− compared with CIMP+
  3. bOther covariates included in the multivariate analysis are differentiation and chemotherapy
  4. cOther covariates included in the multivariate analysis are chemotherapy and radiation therapy
  5. dRelative survival ratio of observed survival rate to the expected survival rate in a population with similar sex and age distribution derived from local mortality
  6. eOriginal paper mentioned the multivariate analysis including all clinical, pathological, and molecular variables
  7. fOther covariates included in the multivariate analysis are adjuvant chemotherapy
  8. gOther covariates included in the multivariate analysis are year of diagnosis, location, and tumor grade
  9. hOther covariates included in the multivariate analysis are Crohn’s-like lymphoid reaction, peritumoral lymphocytic reaction, and postoperative chemotherapy
  10. iOther covariates included in the multivariate analysis are grade, gross type and Crohn’s-like lymphoid reaction, and peritumoral lymphocytic reaction