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Table 3 LINE-1 extreme hypomethylators (< 40) compared to colorectal cancers with LINE-1 methylation level ≥40.

From: Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors

Clinical, pathologic or molecular feature

Total N

LINE-1 methylation level

P value^

  

≥40

< 40

 

All cases

869

847

22

 

Sex

   

1.00

Men

394 (45%)

384 (45%)

10 (45%)

 

Women

475 (55%)

463 (55%)

12 (55%)

 

Age (years)

   

0.0058

< 60

196 (23%)

186 (22%)

10 (45%)

 

60-69

363 (42%)

360 (43%)

3 (14%)

 

≥70

310 (36%)

301 (36%)

9 (41%)

 

Body mass index (BMI, kg/m2)

   

1.00

< 30

667 (83%)

649 (82%)

18 (86%)

 

≥30

141 (17%)

138 (18%)

3 (14%)

 

Family history of colorectal cancer

   

0.80

(-)

657 (76%)

641 (76%)

16 (73%)

 

(+)

212 (24%)

206 (24%)

6 (27%)

 

Smoking status

   

0.082

Never

349 (41%)

336 (40%)

13 (59%)

 

Past or current

508 (59%)

499 (60%)

9 (41%)

 

Tumor location

   

0.094

Proximal colon (cecum to transverse)

370 (44%)

365 (45%)

5 (25%)

 

Distal colon (splenic flexure to sigmoid)

274 (33%)

263 (32%)

11 (55%)

 

Rectum

192 (23%)

188 (23%)

4 (20%)

 

Disease stage

   

0.66

I

196 (25%)

193 (25%)

3 (14%)

 

II

253 (33%)

246 (32%)

7 (33%)

 

III

226 (29%)

218 (29%)

8 (38%)

 

IV

103 (13%)

100 (13%)

3 (14%)

 

Tumor grade

   

0.45

Low

777 (91%)

758 (91%)

19 (86%)

 

High

79 (9.2%)

76 (9.1%)

3 (14%)

 

Mucinous component

   

0.53

0%

554 (65%)

541 (65%)

13 (59%)

 

1-49%

188 (22%)

181 (22%)

7 (32%)

 

≥50%

115 (13%)

113 (14%)

2 (9.1%)

 

Signet ring cell component

   

1.00

0%

796 (93%)

775 (93%)

21 (95%)

 

1-49%

48 (5.6%)

47 (5.6%)

1 (4.5%)

 

≥50%

14 (1.6%)

14 (1.7%)

0

 

Crohn's-like reaction

   

1.00

Absent/mild

584 (90%)

571 (90%)

13 (93%)

 

Moderate/severe

62 (9.6%)

61 (9.7%)

1 (7.1%)

 

Peritumoral lymphocytic reaction

   

0.73

Absent/mild

744 (89%)

725 (89%)

19 (86%)

 

Moderate/severe

93 (11%)

90 (11%)

3 (14%)

 

Tumor infiltrating lymphocytes (TIL)

   

0.73

Absent/mild

740 (89%)

721 (89%)

19 (86%)

 

Moderate/severe

96 (11%)

93 (11%)

3 (14%)

 

MSI status

   

0.76

MSI-low/MSS

728 (85%)

709 (85%)

19 (90%)

 

MSI-high

124 (15%)

122 (15%)

2 (9.5%)

 

CIMP status

   

0.14

CIMP-0

408 (47%)

393 (46%)

15 (68%)

 

CIMP-low

333 (38%)

327 (39%)

6 (27%)

 

CIMP-high

128 (15%)

127 (15%)

1 (4.6%)

 

KRAS mutation

   

0.38

(-)

538 (63%)

522 (63%)

16 (73%)

 

(+)

319 (37%)

313 (37%)

6 (27%)

 

BRAF mutation

   

1.00

(-)

728 (87%)

709 (87%)

19 (90%)

 

(+)

108 (13%)

106 (13%)

2 (9.5%)

 

PIK3CA mutation

   

0.76

(-)

646 (85%)

627 (84%)

19 (90%)

 

(+)

118 (15%)

116 (16%)

2 (9.5%)

 

TP53 expression

   

0.19

(-)

488 (57%)

472 (56%)

16 (73%)

 

(+)

371 (43%)

365 (44%)

6 (27%)

 

CDKN1A

   

0.099

Lost

682 (81%)

661 (81%)

21 (95%)

 

Expressed

158 (19%)

157 (19%)

1 (4.6%)

 

CTNNB1 score*

   

1.00

0-2 (inactive)

482 (64%)

470 (64%)

12 (63%)

 

3-5 (active)

273 (36%)

266 (36%)

7 (37%)

 

PTGS2 expression

   

0.073

(-)

142 (16%)

135 (16%)

7 (32%)

 

(+)

719 (84%)

704 (84%)

15 (68%)

 

FASN expression

   

0.50

(-)

742 (88%)

721 (88%)

21 (95%)

 

(+)

99 (12%)

98 (12%)

1 (4.6%)

 
  1. (%) indicates the proportion of cases with a specific clinical, pathologic or molecular feature among tumors with LINE-1 methylation level ≥ 40 [or tumors with LINE-1 methylation level < 40]. A p value for significance is adjusted to p = 0.0021 by Bonferroni correction for multiple hypothesis testing.
  2. ^ p values were based on Fisher's exact test.
  3. * CTNNB1 score was calculated as previously described [24].
  4. CIMP, CpG island methylator phenotype; MSI, microsatellite instability; MSS, microsatellite stable.
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Molecular Cancer

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