Background
Methods
Patients and tissue samples
Characteristics | Training cohort (n = 228) | Validation cohort (n = 151) | ||
---|---|---|---|---|
No. of patients (%) | No. of patients (%) | |||
Age (years)
| ||||
<60 | 71 | (31.1) | 43 | (28.5) |
≥60 | 157 | (68.9) | 108 | (71.5) |
Sex
| ||||
Female | 95 | (41.7) | 61 | (40.4) |
Male | 133 | (58.3) | 90 | (59.6) |
Tumor location
| ||||
Rectum | 169 | (74.1) | 81 | (53.6) |
Colon | 59 | (25.9) | 70 | (46.4) |
Differentiation grade
| ||||
Well/Moderate | 171 | (75.0) | 114 | (75.5) |
Poor | 57 | (25.0) | 37 | (24.5) |
Tumor size (cm)
| ||||
<5 | 92 | (40.4) | 57 | (37.7) |
≥5 | 136 | (59.6) | 94 | (62.3) |
Local invasion
| ||||
T1-T2 | 44 | (19.3) | 14 | (9.3) |
T3-T4 | 184 | (80.7) | 137 | (90.7) |
Lymph node metastasis
| ||||
N0 | 132 | (57.9) | 84 | (55.6) |
N1 | 64 | (28.1) | 48 | (31.8) |
N2 | 32 | (14.0) | 19 | (12.6) |
TNM stage
| ||||
I | 36 | (15.8) | 10 | (6.6) |
II | 96 | (42.1) | 74 | (49.0) |
III | 96 | (42.1) | 67 | (44.4) |
Death
| ||||
No | 124 | (54.4) | 82 | (54.3) |
Yes | 104 | (45.6) | 69 | (45.7) |
Real-Time qPCR analysis
Western blot analysis
Immunohistochemistry analysis
Statistical analysis
Results
1. Downregulation of CA7 in CRC tissues
2. Correlation of CA7 expression with clinicopathologic features
Training cohort (n = 228) | Validation cohort (n = 151) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Characteristics | CA7 expression | P valuea | CA7 expression | P valuea | ||||||
Low (%) | High (%) | Low (%) | High (%) | |||||||
(n = 116) | (n = 112) | (n = 89) | (n = 62) | |||||||
Age (years)
| 0.267 | 0.622 | ||||||||
<60 | 40 | (34.5) | 31 | (27.7) | 24 | (27.0) | 19 | (30.6) | ||
≥60 | 76 | (65.5) | 81 | (72.3) | 65 | (73.0) | 43 | (69.4) | ||
Sex
| 0.720 | 0.490 | ||||||||
Female | 47 | (40.5) | 48 | (42.9) | 38 | (42.7) | 23 | (37.1) | ||
Male | 69 | (59.5) | 64 | (57.1) | 51 | (57.3) | 39 | (62.9) | ||
Tumor location
| 0.224 | 0.806 | ||||||||
Rectum | 90 | (77.6) | 79 | (70.5) | 47 | (52.8) | 34 | (54.8) | ||
Colon | 26 | (22.4) | 33 | (29.5) | 42 | (47.2) | 28 | (45.2) | ||
Differentiation grade
|
0.006
|
0.046
| ||||||||
Well/Moderate | 78 | (67.2) | 93 | (83.0) | 62 | (69.7) | 52 | (83.9) | ||
Poor | 38 | (32.8) | 19 | (17.0) | 27 | (30.3) | 10 | (16.1) | ||
Tumor size (cm)
| 0.448 | 0.586 | ||||||||
<5 | 44 | (37.9) | 48 | (42.9) | 32 | (36.0) | 25 | (40.3) | ||
≥5 | 72 | (62.1) | 64 | (57.1) | 57 | (64.0) | 37 | (59.7) | ||
Local invasion
| 0.141 | 0.064 | ||||||||
T1-T2 | 18 | (15.5) | 26 | (23.2) | 5 | (5.6) | 9 | (14.5) | ||
T3-T4 | 98 | (84.5) | 86 | (76.8) | 84 | (94.4) | 53 | (85.5) | ||
Lymph node metastasis
|
0.003
|
0.003
| ||||||||
N0 | 56 | (48.3) | 76 | (67.9) | 41 | (46.1) | 43 | (69.4) | ||
N1 | 36 | (31.0) | 28 | (25.0) | 31 | (34.8) | 17 | (27.4) | ||
N2 | 24 | (20.7) | 8 | (7.1) | 17 | (19.1) | 2 | (3.2) | ||
TNM stage
|
0.008
|
0.003
| ||||||||
I | 13 | (11.2) | 23 | (20.5) | 2 | (2.2) | 8 | (12.9) | ||
II | 43 | (37.1) | 53 | (47.3) | 39 | (43.9) | 35 | (56.5) | ||
III | 60 | (51.7) | 36 | (32.2) | 48 | (53.9) | 19 | (30.6) | ||
Death
|
<0.001
|
<0.001
| ||||||||
No | 47 | (40.5) | 77 | (68.8) | 37 | (41.6) | 45 | (72.6) | ||
Yes | 69 | (59.5) | 35 | (31.2) | 52 | (58.4) | 17 | (27.4) |
3. Prognostic values of CA7 expression in CRC patients
Variables | Categories | Univariate analysis | Multivariate analysisb | ||||
---|---|---|---|---|---|---|---|
HR | 95% CI | P valuec | HR | 95% CI | P valuec | ||
Training Cohort
| |||||||
Age (years) | ≥60 / <60 | 2.263 | 1.389-3.687 |
0.001
| 2.770 | 1.691-4.537 |
<0.001
|
Sex | Male / female | 0.878 | 0.596-1.293 | 0.510 | |||
Tumor location | Colon / rectum | 1.401 | 0.923-2.125 | 0.113 | |||
Tumor size (cm) | ≥5 / <5 | 1.114 | 0.753-1.648 | 0.590 | |||
Differentiation grade | Poor / well + moderate | 2.626 | 1.761-3.916 |
<0.001
| 2.010 | 1.337-3.023 |
0.001
|
TNM stage | III / I+ II | 2.734 | 1.846-4.048 |
<0.001
| 2.402 | 1.603-3.598 |
<0.001
|
CA7 expressiona | Low / high | 2.469 | 1.642-3.717 |
<0.001
| 2.247 | 1.481-3.401 |
<0.001
|
Validation Cohort
| |||||||
Age (years) | ≥60 / <60 | 1.976 | 1.080-3.614 |
0.027
| 2.293 | 1.247-4.217 |
0.008
|
Sex | Male / female | 0.737 | 0.459-1.183 | 0.207 | |||
Tumor location | Colon / rectum | 0.961 | 0.599-1.542 | 0.868 | |||
Tumor size (cm) | ≥5 / <5 | 0.814 | 0.503-1.317 | 0.403 | |||
Differentiation grade | Poor / well + moderate | 1.688 | 1.017-2.803 |
0.043
| |||
TNM stage | III / I+ II | 2.828 | 1.734-4.611 |
<0.001
| 2.674 | 1.615-4.428 |
<0.001
|
CA7 expressiona | Low / high | 2.632 | 1.520-4.545 |
0.001
| 2.058 | 1.174-3.610 |
0.012
|
Variables | Categories | Early stage | Advanced stage | ||||
---|---|---|---|---|---|---|---|
HR | 95% CI | P valueb | HR | 95% CI | P valueb | ||
Training Cohort
| |||||||
Age (years) | ≥60 / <60 | 4.062 | 1.592-10.365 |
0.003
| 2.353 | 1.282-4.319 |
0.006
|
Sex | Male / female | ||||||
Tumor location | Colon / rectum | ||||||
Tumor size (cm) | ≥5 / <5 | ||||||
Differentiation grade | Poor / well + moderate | 2.389 | 1.419-4.023 |
0.001
| |||
CA7 expressiona | Low / high | 2.232 | 1.220-4.082 |
0.009
| 2.809 | 1.524-5.181 |
0.001
|
Validation Cohort
| |||||||
Age (years) | ≥60 / <60 | 2.374 | 1.176-4.794 |
0.016
| |||
Sex | Male / female | ||||||
Tumor location | Colon / rectum | ||||||
Tumor size (cm) | ≥5 / <5 | ||||||
Differentiation grade | Poor / well + moderate | 2.637 | 1.414-4.920 |
0.002
| |||
CA7 expressiona | Low / high | 3.165 | 1.326-7.519 |
0.009
|