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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.