Table 1.
Patient characteristics.
| TNM stage | ||||
|---|---|---|---|---|
| Characteristica | All cases (N = 815) | Stage II (N = 453) | Stage III (N = 362) | P valueb |
| Sex | 0.036 | |||
| Female (NHS) | 502 (62%) | 294 (65%) | 208 (57%) | |
| Male (HPFS) | 313 (38%) | 159 (35%) | 154 (43%) | |
| Mean age ± SD (years) | 68.6 ± 8.9 | 68.9 ± 8.7 | 68.1 ± 9.1 | 0.22 |
| Family history of colorectal cancer in any first-degree relative | 0.73 | |||
| No | 660 (81%) | 365 (81%) | 295 (82%) | |
| Yes | 152 (19%) | 87 (19%) | 65 (18%) | |
| Pack-years of smoking at diagnosis | 0.24 | |||
| 0 | 328 (42%) | 174 (40%) | 154 (44%) | |
| 1–19 | 178 (23%) | 94 (22%) | 84 (24%) | |
| 20–39 | 137 (18%) | 80 (18%) | 57 (16%) | |
| ≥40 | 137 (18%) | 85 (20%) | 52 (15%) | |
| Tumor location | 0.23 | |||
| Cecum | 136 (17%) | 76 (17%) | 60 (17%) | |
| Ascending to transverse colon | 288 (36%) | 173 (38%) | 115 (32%) | |
| Descending to sigmoid colon | 277 (34%) | 146 (32%) | 131 (36%) | |
| Rectum | 108 (13%) | 55 (12%) | 53 (15%) | |
| Tumor differentiation | 0.077 | |||
| Well to moderate | 709 (87%) | 403 (89%) | 306 (85%) | |
| Poor | 106 (13%) | 50 (11%) | 56 (15%) | |
| Tumor depth of invasion (pT stage) | <0.0001 | |||
| pT1 | 13 (2%) | 0 (0%) | 13 (4%) | |
| pT2 | 45 (5%) | 0 (0 %) | 47 (13%) | |
| pT3 | 704 (87%) | 423 (93%) | 281 (78%) | |
| pT4 | 49 (6%) | 30 (7%) | 19 (5%) | |
| Positive lymph node count | <0.0001 | |||
| 0 (pN0) | 416 (56%) | 416 (100%) | 0 (0%) | |
| 1–3 (pN1) | 228 (30%) | 0 (0%) | 228 (69%) | |
| ≥4 (pN2) | 103 (14%) | 0 (0%) | 103 (31%) | |
| Negative lymph node count | <0.0001 | |||
| 0–5 | 144 (21%) | 55 (15%) | 89 (28%) | |
| 6–11 | 243 (35%) | 125 (34%) | 118 (37%) | |
| 12–17 | 137 (20%) | 77 (21%) | 60 (19%) | |
| ≥18 | 170 (24%) | 114 (31%) | 56 (17%) | |
| Extent of extraglandular necrosis | 0.29 | |||
| 0% | 509 (62%) | 285 (63%) | 224 (62%) | |
| 1–19% | 167 (20%) | 85 (19%) | 82 (23%) | |
| ≥20% | 139 (17%) | 83 (18%) | 56 (15%) | |
| Lymphovascular invasion | 0.003 | |||
| None | 538 (90%) | 320 (94%) | 218 (86%) | |
| Mild | 35 (6%) | 13 (4%) | 22 (9%) | |
| Moderate/extensive | 21 (4%) | 7 (2%) | 14 (6%) | |
| Perineural invasion | 0.009 | |||
| None | 575 (98%) | 333 (99%) | 242 (96%) | |
| Mild | 8 (1%) | 3 (0.9%) | 5 (2%) | |
| Moderate/extensive | 5 (0.9%) | 0 (0%) | 5 (2%) | |
| Extracellular mucinous component | 0.004 | |||
| 0% | 448 (57%) | 232 (53%) | 216 (62%) | |
| 1–49% | 193 (25%) | 107 (25%) | 86 (25%) | |
| ≥50% | 143 (18%) | 97 (22%) | 46 (13%) | |
| Signet ring cell component | 0.24 | |||
| 0% | 677 (87%) | 383 (88%) | 294 (84%) | |
| 1–9% | 75 (10%) | 35 (8%) | 40 (11%) | |
| ≥10% | 29 (4%) | 15 (3%) | 14 (4%) | |
| Tumor-infiltrating lymphocytes (TILs) | 0.003 | |||
| Absent/minimal | 558 (72%) | 294 (68%) | 264 (76%) | |
| Mild | 123 (16%) | 69 (16%) | 54 (16%) | |
| Moderate/severe | 96 (12%) | 68 (16%) | 28 (8%) | |
| MSI status | <0.0001 | |||
| Non-MSI-high | 556 (80%) | 279 (73%) | 277 (88%) | |
| MSI-high | 143 (20%) | 104 (27%) | 39 (12%) | |
| CIMP status | 0.0004 | |||
| Low/negative | 520 (75%) | 268 (70%) | 252 (82%) | |
| High | 174 (25%) | 117 (30%) | 57 (18%) | |
| Mean LINE-1 methylation level ± SD (%) | 63.7 ± 10.2 | 64.3 ± 10.0 | 62.9 ± 10.3 | 0.069 |
| KRAS mutation | 0.10 | |||
| Wild-type | 390 (58%) | 224 (61%) | 166 (55%) | |
| Mutant | 278 (42%) | 141 (39%) | 137 (45%) | |
| BRAF mutation | 0.15 | |||
| Wild-type | 584 (83%) | 314 (81%) | 270 (85%) | |
| Mutant | 122 (17%) | 75 (19%) | 47 (15%) | |
| PIK3CA mutation | 0.38 | |||
| Wild-type | 550 (84%) | 293 (83%) | 257 (85%) | |
| Mutant | 106 (16%) | 62 (17%) | 44 (15%) | |
| Memory cytotoxic T-cell (CD3+CD8+CD45RO+ cell) densityc | 0.014 | |||
| Q0 (0, lowest) | 244 (48%) | 115 (42%) | 139 (56%) | |
| Q1 | 88 (17%) | 56 (20%) | 32 (14%) | |
| Q2 | 88 (17%) | 53 (19%) | 35 (15%) | |
| Q3 (highest) | 88 (17%) | 53 (19%) | 35 (15%) | |
| Memory helper T-cell (CD3+CD4+CD45RO+ cell) densityc | 0.51 | |||
| Q0 (0, lowest) | 176 (34%) | 89 (32%) | 87 (37%) | |
| Q1 | 111 (22%) | 64 (23%) | 47 (20%) | |
| Q2 | 111 (22%) | 65 (23%) | 46 (20%) | |
| Q3 (highest) | 110 (22%) | 59 (21%) | 51 (22%) | |
| Fusobacterium nucleatum in tumor | 0.34 | |||
| Negative | 572 (85%) | 309 (83%) | 263 (86%) | |
| Positive | 104 (15%) | 62 (17%) | 42 (14%) | |
| Bifidobacterium species in tumor | 0.46 | |||
| Negative | 485 (70%) | 269 (71%) | 216 (68%) | |
| Positive | 211 (30%) | 110 (29%) | 101 (32%) | |
| Five-year colorectal cancer-specific survival status | <0.0001 | |||
| Survival | 661 (81%) | 392 (87%) | 269 (74%) | |
| Death | 154 (19%) | 61 (13%) | 93 (26%) | |
AJCC American Joint Committee on Cancer, CIMP CpG island methylator phenotype, HPFS Health Professionals Follow-up Study, LINE-1 long-interspersed nucleotide element-1, MSI microsatellite instability, NHS Nurses’ Health Study, SD standard deviation, TNM tumor-node-metastasis.
aPercentage indicates the proportion of patients with a specific clinical, pathologic, or molecular characteristic among all patients or in strata of the stage, excluding missing data.
bTo compare categorical data between stages, the Chi-square test was performed. To compare continuous variables, analysis of variance (ANOVA) was performed for variables exhibiting normality. For variables that did not follow a normal distribution, values were separated into ordinal categories prior to the Chi-square test. For lymphovascular invasion and perineural invasion, Fisher’s exact tests were performed.
cTumor tissue CD3+CD8+CD45RO+ and CD3+CD4+CD45RO+ cell density measures (cells/mm2) were categorized into 0 value (the lowest category, Q0) and positive values divided equally into tertiles (Q1 to Q3).
Clinical, pathologic, molecular, and immune characteristics of patients with colorectal cancer according to AJCC TNM staging.