Background
Methods
Patients
Tumor samples
Analysis of protein expression
Patients’ clinicopathological characteristics
Characteristics | Patients (n) | Patients (%) |
---|---|---|
Age (years) | ||
< 50 | 10 | 15.9 |
≥ 50 | 53 | 84.1 |
Unknown | - | - |
Tumor size (cm) | ||
<2 | 45 | 71.4 |
≥ 2 | 17 | 27.0 |
Unknown | 1 | 1.6 |
Histological grade | ||
G1 | 15 | 23.8 |
G2 | 22 | 34.9 |
G3 | 24 | 38.1 |
Unknown | 2 | 3.2 |
HER2/neu status | ||
Negative | 39 | 61.9 |
Positive | 23 | 36.5 |
Unknown | 1 | 1.6 |
ER status | ||
Negative | 15 | 23.8 |
Positive | 47 | 74.6 |
Unknown | 1 | 1.6 |
PR status | ||
Negative | 14 | 22.2 |
Positive | 48 | 76.2 |
Unknown | 1 | 1.6 |
Regional lymph nodes | ||
Negative | 44 | 69.8 |
Positive | 16 | 25.4 |
Unknown | 3 | 4.8 |
Local relapse | ||
Negative | 50 | 79.4 |
Positive | 6 | 9.5 |
Unknown | 7 | 11.1 |
Metastatic event | ||
Non-metastasis | 45 | 71.4 |
Metastasis | 11 | 17.5 |
Unknown | 7 | 11.1 |
Statistical analysis
Results
Association of expression in TEpCs of OPG, TRAIL, RANKL, SDF-1, IL-6, and CCL-2 with patients’ clinicopathological characteristics
Characteristics | Ligands in TEpC | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
OPG | TRAIL | RANKL | SDF-1 | IL-6 | CCL-2 | ||||||||
High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| ||
Age (years) | <50 | 10.0 | >0.999 | 2.2 | 0.657 | 70.0 | >0.999 | 40.0 | 0.153 | 22.2 | 0.464 | 22.2 | 0.110 |
≥50 | 15.7 | 16.0 | 73.1 | 67.3 | 39.2 | 4.1 | |||||||
Tumor size (cm) | <2 | 13.9 | >0.999 | 17.1 | >0.999 | 65.9 | 0.114 | 70.4 | 0.044* | 42.9 | 0.236 | 7.3 | >0.999 |
≥2 | 11.8 | 17.6 | 88.2 | 41.2 | 23.5 | 6.2 | |||||||
Histological grade | G1 | 20.0 | 0.713 | 21.4 | 0.744 | 46.7 | 0.073 | 80.0 | 0.093 | 42.9 | 0.307 | 6.7 | 0.357 |
G2 | 10.0 | 20.0 | 80.9 | 66.7 | 45.0 | 0.0 | |||||||
G3 | 12.5 | 13.0 | 79.2 | 45.8 | 25.0 | 13.0 | |||||||
HER2/neu status | Negative | 8.1 | 0.239 | 18.9 | 0.733 | 76.3 | 0.388 | 63.2 | >0.999 | 39.5 | 0.780 | 2.9 | 0.287 |
Positive | 21.7 | 14.3 | 65.2 | 60.9 | 33.33 | 13.6 | |||||||
ER status | Negative | 13.3 | >0.999 | 7.7 | 0.429 | 80.0 | 0.523 | 40.0 | 0.064 | 42.9 | 0.753 | 20.0 | 0.049* |
Positive | 13.3 | 20.0 | 69.6 | 69.6 | 35.6 | 2.4 | |||||||
PR status | Negative | 14.3 | >0.999 | 8.3 | 0.444 | 78.6 | 0.737 | 50.0 | 0.351 | 38.5 | >0.999 | 7.1 | >0.999 |
Positive | 13.0 | 19.6 | 70.2 | 66.0 | 37.0 | 7.0 | |||||||
Regional lymph nodes | Negative | 11.6 | 0.666 | 25.0 | 0.048* | 67.4 | 0.352 | 58.1 | 0.555 | 39.0 | 0.761 | 4.7 | 0.349 |
Positive | 20.0 | 0.0 | 81.2 | 68.7 | 31.2 | 14.3 | |||||||
Metastatic occurrence | Negative | 20.9 | 0.180 | 21.4 | 0.664 | 70.4 | 0.707 | 59.1 | >0.999 | 30.2 | >0.999 | 2.4 | 0.109 |
Positive | 18.2 | 10.0 | 81.8 | 63.6 | 40.0 | 18.2 | |||||||
Local relapse | Negative | 6.1 | 0.330 | 20.8 | 0.576 | 70.0 | 0.307 | 60.0 | >0.999 | 38.8 | 0.284 | 4.3 | 0.266 |
Positive | 20.0 | 0.0 | 100.0 | 60.0 | 0.0 | 20.0 |
Univariate |
p-value | ||
---|---|---|---|
Disease-free survival | Metastasis-free survival | Overall survival | |
Age | 0.598 | 0.448 | 0.500 |
Tumor size | 0.113 | 0.020* | 0.069 |
Histological grade | 0.178 | 0.291 | 0.207 |
HER2/neu status | 0.536 | 0.293 | 0.103 |
ER status | 0.336 | 0.191 | 0.175 |
PR status | 0.691 | 0.946 | 0.521 |
Regional lymph nodes | 0.595 | 0.805 | 0.620 |
OPG/TEpC | 0.167 | 0.052 | 0.178 |
TRAIL/TEpC | 0.465 | 0.648 | 0.304 |
RANKL/TEpC | 0.156 | 0.267 | 0.307 |
SDF-1/TEpC | 0.660 | 0.932 | 0.710 |
IL-6/TEpC CCL-2 | 0.873 | 0.710 | 0.487 |
CCL-2/TEpC | 0.048* | 0.071 | 0.507 |
TRAIL-R1/TEpC | 0.536 | 0.339 | 0.626 |
TRAIL-R2/TEpC | 0.894 | 0.749 | 0.392 |
TRAIL-R3/TEpC | 0.009* | 0.012* | 0.015* |
TRAIL-R4/TEpC | 0.186 | 0.131 | 0.478 |
RANK/TEpC | 0.546 | 0.991 | 0.804 |
CXCR-4/TEpC | 0.164 | 0.255 | 0.175 |
IL-6R/TEpC | 0.391 | 0.540 | 0.626 |
CCR-2/TEpC | 0.013* | 0.002* | 0.049* |
OPG/stromal cells | 0.318 | 0.101 | 0.441 |
TRAIL/stromal cells | 0.284 | 0.084 | 0.337 |
RANKL/stromal cells | 0.139 | 0.052 | 0.222 |
SDF-1/stromal cells | 0.792 | 0.734 | 0.306 |
IL-6/stromal cells CCL-2 | 0.218 | 0.093 | 0.168 |
CCL-2/stromal cells | 0.104 | 0.076 | 0.505 |
Association of expression in TEpCs of TRAIL-R1–4, RANK, CXCR-4, IL-6R, and CCR-2 with patients’ clinicopathological characteristics
Characteristics | Receptors in TEpC | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
TRAIL-R1 | TRAIL-R2 | TRAIL-R3 | TRAIL-R4 | RANK | CXCR-4 | IL-6-R | CCR-2 | ||||||||||
High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| ||
Age (years) | <50 | 87.5 | 0.249 | 0.0 | >0.999 | 40.0 | 0.729 | 80.0 | 0.175 | 30.0 | 0.176 | 50.0 | 0.259 | 75.0 | 0.042* | 11.1 | >0.999 |
≥50 | 63.5 | 9.6 | 34.0 | 54.7 | 55.8 | 73.1 | 31.3 | 12.0 | |||||||||
Tumor size (cm) | <2 | 66.7 | >0.999 | 9.3 | >0.999 | 35.6 | >0.999 | 57.8 | >0.999 | 50.0 | 0.579 | 68.2 | >0.999 | 31.6 | 0.365 | 11.9 | >0.999 |
≥2 | 64.7 | 5.9 | 35.3 | 58.8 | 58.8 | 70.6 | 47.1 | 12.5 | |||||||||
Histological grade | G1 | 71.4 | 0.397 | 13.3 | 0.245 | 33.3 | >0.999 | 60.0 | 0.803 | 53.3 | >0.999 | 66.7 | 0.941 | 38.5 | 0.078 | 20.0 | 0.597 |
G2 | 55.0 | 0.0 | 36.7 | 63.6 | 52.4 | 71.4 | 16.7 | 10.0 | |||||||||
G3 | 75.0 | 12.5 | 37.5 | 54.2 | 50.0 | 66.7 | 50.0 | 8.7 | |||||||||
HER2/neu status | Negative | 59.5 | 0.255 | 5.4 | 0.361 | 25.6 | 0.054 | 51.3 | 0.190 | 52.6 | >0.999 | 71.0 | 0.776 | 26.5 | 0.083 | 16.7 | 0.235 |
Positive | 77.3 | 13.0 | 52.2 | 69.6 | 52.2 | 65.2 | 52.4 | 4.5 | |||||||||
ER status | Negative | 66.7 | >0.999 | 13.3 | 0.590 | 53.3 | 0.125 | 60.0 | >0.999 | 60.0 | 0.562 | 73.3 | 0.757 | 46.7 | 0.361 | 20.0 | 0.359 |
Positive | 65.9 | 6.7 | 29.8 | 57.4 | 50.0 | 67.4 | 32.5 | 9.3 | |||||||||
PR status | Negative | 64.3 | >0.999 | 14.3 | 0.581 | 42.9 | 0.539 | 57.1 | >0.999 | 57.1 | 0.766 | 78.6 | 0.516 | 35.7 | >0.999 | 14.3 | >0.999 |
Positive | 66.7 | 6.5 | 33.3 | 58.3 | 51.1 | 66.0 | 36.6 | 11.4 | |||||||||
Regional lymph nodes | Negative | 64.3 | 0.342 | 9.3 | >0.999 | 36.4 | >0.999 | 61.4 | 0.771 | 55.8 | 0.558 | 72.1 | 0.533 | 35.0 | 0.749 | 11.9 | >0.999 |
Positive | 80.0 | 6.7 | 37.5 | 56.2 | 43.7 | 62.5 | 42.9 | 13.3 | |||||||||
Metastatic occurrence | Negative | 66.7 | 0.108 | 4.6 | 0.502 | 26.7 | 0.032* | 51.1 | 0.092 | 50.0 | >0.999 | 70.4 | 0.473 | 30.8 | 0.171 | 4.8 | 0.003* |
Positive | 90.9 | 9.1 | 63.6 | 81.8 | 45.4 | 54.5 | 54.5 | 45.4 | |||||||||
Local relapse | Negative | 70.8 | >0.999 | 4.1 | 0.257 | 31.4 | 0.323 | 56.9 | >0.999 | 48.0 | 0.669 | 70.0 | 0.316 | 35.6 | >0.999 | 14.6 | 0.601 |
Positive | 80.0 | 20.0 | 60.0 | 60.0 | 60.0 | 40.0 | 40.0 | 0.0 |
Association of expression in spindle-shaped stromal cells of OPG, TRAIL, RANKL, SDF-1, IL-6, and CCL-2 with patients’ clinicopathological characteristics
Characteristics | Ligands in spindle-shaped stromal cells | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
OPG | TRAIL | RANKL | SDF-1 | IL-6 | CCL-2 | ||||||||
High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| High expression % |
p
| ||
Age (years) | <50 | 50.0 | 0.742 | 66.7 | 0.137 | 70.0 | 0.709 | 40.0 | 0.493 | 22.2 | 0.664 | 22.2 | 0.646 |
≥50 | 44.0 | 35.3 | 75.0 | 55.8 | 17.6 | 16.3 | |||||||
Tumor size (cm) | <2 | 48.8 | 0.255 | 38.1 | >0.999 | 68.2 | 0.193 | 56.8 | 0.391 | 21.4 | 0.483 | 19.5 | 0.708 |
≥2 | 31.2 | 41.2 | 88.2 | 41.2 | 11.8 | 12.5 | |||||||
Histological grade | G1 | 60.0 | 0.336 | 35.7 | 0.518 | 60.0 | 0.491 | 66.7 | 0.042* | 21.4 | 0.741 | 33.3 | 0.116 |
G2 | 35.0 | 50.0 | 76.2 | 66.7 | 20.0 | 5.3 | |||||||
G3 | 39.1 | 33.3 | 79.2 | 33.3 | 12.5 | 17.4 | |||||||
HER2/neu status | Negative | 44.4 | >0.999 | 44.7 | 0.272 | 78.9 | 0.368 | 57.9 | 0.302 | 18.4 | >0.999 | 17.1 | >0.999 |
Positive | 43.5 | 28.6 | 65.2 | 43.5 | 19.0 | 18.2 | |||||||
ER status | Negative | 46.7 | >0.999 | 42.9 | 0.761 | 80.0 | 0.738 | 53.3 | >0.999 | 21.4 | >0.999 | 20.0 | >0.999 |
Positive | 43.2 | 37.8 | 71.7 | 52.2 | 17.8 | 16.7 | |||||||
PR status | Negative | 42.9 | >0.999 | 30.8 | 0.540 | 78.6 | 0.742 | 50.0 | >0.999 | 15.4 | >0.999 | 7.1 | 0.422 |
Positive | 44.4 | 41.3 | 72.3 | 53.2 | 19.6 | 20.9 | |||||||
Regional lymph nodes | Negative | 46.1 | 0.547 | 41.5 | >0.999 | 74.4 | 0.745 | 55.8 | 0.773 | 17.1 | >0.999 | 19.0 | 0.724 |
Positive | 35.7 | 37.5 | 68.7 | 50.0 | 18.7 | 14.3 | |||||||
Metastatic occurrence | Negative | 32.5 | 0.038* | 34.9 | 0.072 | 65.9 | 0.146 | 47.3 | 0.745 | 11.6 | 0.163 | 9.1 | 0.049* |
Positive | 70.0 | 70.0 | 90.9 | 54.5 | 30.0 | 36.4 | |||||||
Local relapse | Negative | 39.6 | >0.999 | 42.9 | 0.633 | 72.0 | 0.621 | 50.0 | >0.999 | 16.3 | 0.612 | 14.9 | >0.999 |
Positive | 40.0 | 25.0 | 60.0 | 40.0 | 0.0 | 20.0 |
Univariate analysis of the association of classical prognostic markers with DFS, MFS, and OS
Multivariate analysis
Variables | HR | 95% CI |
p
| |
---|---|---|---|---|
Disease-free survival | TRAIL-R3 in TEpC | 3.566 | 1.164–10.920 | 0.026 |
Metastasis-free survival | Tumor size | 8.210 | 2.013–33.477 | 0.003 |
CCR-2 in TEpC | 10.257 | 2.569–40.947 | 0.001 | |
Overall survival | TRAIL-R3 in TEpC | 5.741 | 1.113–29.621 | 0.037 |