Introduction
Materials and methods
Patients
Tissue microarray (TMA) construction
Immunohistochemistry (IHC)
Statistical analyses
Results
Clinical characteristics
Variable | Total cases | PD-L1TPS* | P-value (r*) | PD-L1ICS* | P-value (r) | PD-L1CPS* | P-value (r*) | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
Positive | Negative | Positive | Negative | Positive | Negative | ||||||
Age (years) | < 45 | 45 | 26 | 19 | 0.830 | 16 | 29 | 0.823 | 32 | 13 | 0.652 |
≥ 45 | 44 | 27 | 17 | (0.037) | 14 | 30 | (− 0.04) | 29 | 15 | (− 0.056) | |
FIGO* stage | I-II | 53 | 33 | 20 | 0.660 | 18 | 35 | 1.000 | 35 | 18 | 0.644 |
III-IV | 36 | 20 | 16 | (− 0.067) | 12 | 24 | (− 0.007) | 26 | 10 | (0.065) | |
Tumor size(cm) | < 2 | 11 | 7 | 4 | 0.923 (− 0.043) | 4 | 7 | 0.932 | 7 | 4 | 0.881 |
≥ 2, < 4 | 38 | 23 | 15 | 12 | 26 | (0.008) | 27 | 11 | (-0.003) | ||
≥ 4 | 40 | 23 | 17 | 14 | 26 | 27 | 13 | ||||
NSE(U/ml) | ≤ 15.2 | 55 | 31 | 24 | 0.804 | 13 | 42 | 0.179 | 37 | 18 | 1.000 |
> 15.2 | 23 | 14 | 9 | (0.042) | 9 | 14 | (0.157) | 16 | 7 | (0.022) | |
Stromal invasion | < 1/2 | 33 | 22 | 11 | 0.373 | 12 | 21 | 0.817 | 24 | 9 | 0.638 |
≥ 1/2 | 56 | 31 | 25 | (− 0.111) | 18 | 38 | (− 0.043) | 37 | 19 | (− 0.069) | |
Lymphatic metastasis | No | 53 | 33 | 20 | 0.660 | 18 | 35 | 1.000 | 35 | 18 | 0.644 |
Yes | 36 | 20 | 16 | (− 0.067) | 12 | 24 | (− 0.007) | 26 | 10 | (0.065) | |
Parametrium invasion | No | 78 | 48 | 30 | 0.341 | 27 | 51 | 0.744 | 55 | 23 | 0.312 |
Yes | 11 | 5 | 6 | (− 0.108) | 3 | 8 | (− 0.051) | 6 | 5 | (− 0.113) | |
LVSI* | No | 15 | 8 | 7 | 0.770 | 5 | 10 | 0.760 | 10 | 5 | 0.760 |
Yes | 58 | 35 | 23 | (0.058) | 17 | 41 | (− 0.035) | 41 | 17 | (0.035) | |
PNI* | No | 42 | 26 | 16 | 0.788 | 8 | 34 | 0.070 | 30 | 12 | 0.774 |
Yes | 21 | 12 | 9 | (− 0.046) | 9 | 12 | (0.253) | 14 | 7 | (− 0.049) | |
HPV* Infection | Positive | 50 | 32 | 18 | 0.145 | 16 | 34 | 1.000 | 37 | 1 | 0.028 |
Negative | 5 | 1 | 4 | (0.258) | 1 | 4 | (0.075) | 13 | 4 | (0.336) | |
P16 | Yes | 76 | 48 | 28 | 0.128 | 24 | 52 | 0.349 | 55 | 21 | 0.102 |
No | 13 | 5 | 8 | (0.178) | 6 | 7 | (− 0.109) | 6 | 7 | (0.199) | |
Ki67 | ≥ 70% | 53 | 27 | 26 | 1.000 | 11 | 35 | 0.048 | 33 | 28 | 0.648 |
< 70% | 46 | 19 | 17 | − 0.018 | 19 | 24 | (− 0.214) | 13 | 15 | (0.071) | |
MMR | dMMR* | 17 | 12 | 5 | 0.412 | 5 | 12 | 0.781 | 12 | 5 | 1.000 |
pMMR* | 72 | 41 | 31 | (0.109) | 25 | 47 | (− 0.041) | 49 | 23 | (0.021) | |
NACT* | Yes | 32 | 18 | 14 | 0.659 | 16 | 16 | 0.02 | 23 | 9 | 0.643 |
No | 57 | 35 | 22 | (− 0.05) | 14 | 43 | (0.258) | 38 | 19 | (0.054) | |
Postoperative therapy | No | 5 | 4 | 1 | 0.644 | 2 | 3 | 1.000 | 4 | 1 | 1.000 |
Yes | 84 | 49 | 35 | (− 0.102) | 28 | 56 | (− 0.032) | 57 | 27 | (− 0.06) | |
Tumor recurrence | No | 48 | 33 | 15 | 0.083 (− 0.203) | 22 | 26 | 0.013 (− 0.278) | 11 | 37 | 0.071 (− 0.199) |
Yes | 41 | 20 | 21 | 8 | 33 | 17 | 24 | ||||
Vital status | Alive | 59 | 40 | 19 | 0.039 (− 0.236) | 23 | 36 | 0.162 (− 0.156) | 16 | 12 | 0.003 (− 0.336) |
Dead | 30 | 13 | 17 | 7 | 1 | 14 | 47 |
Immunohistochemical assessment
Variable | Total cases | PD-L1TPS* | P-value (r*) | PD-L1ICS* | P-value (r*) | PD-L1CPS* | P-value (r*) | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
Positive | Negative | Positive | Negative | Positive | Negative | ||||||
CD20 | Positive | 51 | 37 | 14 | 0.005 (0.307) | 25 | 25 | < 0.001 (0.390) | 42 | 8 | 0.001 (0.377) |
Negative | 38 | 16 | 22 | 5 | 34 | 19 | 20 | ||||
CD4 | High | 46 | 36 | 10 | 0.000 (0.394) | 18 | 28 | 0.370 (0.119) | 42 | 4 | < 0.001 (0.507) |
Low | 43 | 17 | 26 | 12 | 31 | 19 | 24 | ||||
CD8 | High | 45 | 36 | 9 | < 0.001 (0.421) | 26 | 19 | < 0.001 (0.515) | 41 | 4 | < 0.001 (0.492) |
Low | 44 | 17 | 27 | 4 | 40 | 20 | 24 | ||||
CD68 | High | 63 | 42 | 21 | 0.056 (0.226) | 21 | 42 | 1.000 (− 0.12) | 49 | 14 | 0.006 (0.310) |
Low | 26 | 11 | 15 | 9 | 17 | 12 | 14 | ||||
CD3 | High | 45 | 37 | 8 | < 0.001 (0.467) | 23 | 22 | 0.001 (0.372) | 42 | 3 | < 0.001 (0.540) |
Low | 44 | 16 | 28 | 7 | 37 | 19 | 25 | ||||
TILs | High | 59 | 44 | 15 | < 0.001 | 20 | 39 | 1.000 | 48 | 11 | 0.001 |
Low | 30 | 9 | 21 | (0.429) | 10 | 20 | (0.006) | 13 | 17 | (0.387) | |
PD-L1 TPS | 53 | 53 | 0 | – | 24 | 29 | 0.006 (0.297) | 53 | 0 | < 0.001 (0.822) | |
Neg | 36 | 0 | 36 | 6 | 30 | 8 | 28 | ||||
PD-L1 ICS | Positive | 30 | 24 | 6 | 0.006 | 30 | 0 | – | 26 | 4 | 0.009 |
Negative | 59 | 29 | 30 | (0.297) | 0 | 59 | 35 | 24 | (0.278) | ||
PD-L1 CPS | Positive | 61 | 53 | 8 | < 0.001 | 26 | 35 | 0.009 | 61 | 0 | – |
Neg | 28 | 0 | 28 | (0.822) | 4 | 24 | (0.278) | 0 | 28 | ||
PD-1 | Positive | 45 | 33 | 12 | 0.01 (0.284) | 23 | 22 | 0.001 (0.372) | 40 | 5 | < 0.001 (0.443) |
Negative | 44 | 20 | 24 | 7 | 37 | 21 | 23 | ||||
FOXP3 | High | 56 | 43 | 13 | < 0.001 (0.457) | 25 | 31 | 0.005 (0.301) | 49 | 7 | < 0.001 (0.532) |
Low | 33 | 10 | 23 | 5 | 28 | 12 | 21 |
Correlation of PD-L1 with clinicopathological features
Correlation of PD-L1 with TAICs
Prognostic significance of PD-L1
Variables | OS | DFS | ||
---|---|---|---|---|
HR (95% CI) | P value | HR (95% CI) | P value | |
Age (years)(< 45 vs. ≥ 45) | 1.035 (0.506–2.119) | 0.924 | 0.993 (0.534–1.847) | 0.983 |
Tumor size(cm)(< 2 vs. ≥ 2, < 4 vs. ≥ 4) | 1.658 (0.919–2.993) | 0.093 | 1.254 (0.770–2.042) | 0.364 |
NSE(U/ml) (≤ 15.2 vs. > 15.2) | 2.275 (1.046–4.947) | 0.038 | 1.037 (0.498–2.161) | 0.922 |
HPV* Infection(Positive vs. Negative) | 0.377 (0.109–1.298) | 0.122 | 0.364 (0.107–1.238) | 0.106 |
FIGO* stage (I–II vs. III–IV) | 2.033 (0.991–4.170) | 0.048 | 1.571 (0.842–2.933) | 0.156 |
Stromal invasion (< 1/2 vs. ≥ 1/2) | 1.965 (0.874–4.420) | 0.102 | 2.152 (1.073–4.315) | 0.031 |
Lymphatic metastasis (No vs. Yes) | 2.033 (0.991–4.170) | 0.053 | 1.571 (0.842–2.933) | 0.156 |
Parametrium invasion (No vs. Yes) | 3.251 (1.384–7.633) | 0.004 | 2.849 (1.253–6.476) | 0.012 |
LVSI* (No vs. Yes vs. Na) | 6.489 (0.871–48.312) | 0.068 | 3.750 (1.142–12.311) | 0.029 |
PNI* (No vs. Yes vs. Na) | 4.479 (1.834–10.938) | 0.001 | 3.065 (1.520–6.182) | 0.002 |
NACT* (Yes vs. No) | 1.716 (0.837–3.521) | 0.141 | 0.998 (0.520–1.916) | 0.995 |
Postoperative therapy (No vs. Yes) | 0.749 (0.100–5.620) | 0.779 | 0.292 (0.102–0.831) | 0.021 |
P16(No vs. Yes) | 0.994 (0.380–2.602) | 0.991 | 1.081 (0.454–2.578) | 0.860 |
Ki67 (≥ 70% vs. < 70%) MMR(dMMR* vs. pMMR*) CD20 (Positive vs. Negative) | 0.555 (0.259–1.189) | 0.130 | 0.818 (0.438–1.528) | 0.529 |
0.687 (0.262–1.797) | 0.444 | 0.580 (0.243–1.384) | 0.219 | |
0.839 (0.408–1.722) | 0.631 | 0.761 (0.410–1.416) | 0.389 | |
CD 4 (High vs. Low) | 0.761 (0.365–1.588) | 0.466 | 0.997 (0.535–1.857) | 0.992 |
CD 8 (High vs. Low) | 0.728 (0.353–1.504) | 0.392 | 0.692 (0.370–1.297) | 0.251 |
CD68 (High vs. Low) | 0.928 (0.434–1.986) | 0.849 | 1.146 (0.572–2.294) | 0.701 |
CD3 (High vs. Low) | 0.586 (0.278–1.234) | 0.160 | 0.685 (0.366–1.283) | 0.238 |
TILs(High vs. Low) | 0.961 (0.460–2.009) | 0.916 | 1.081 (0.556–2.098) | 0.819 |
PD-1(Positive vs. Negative) | 0.933 (0.455–1.911) | 0.850 | 1.055 (0.567–1.964) | 0.866 |
FOXP3(High vs. Low) | 0.686 (0.332–1.416) | 0.308 | 0.756 (0.403–1.417) | 0.383 |
PD-L1TPS* (Positive vs. Negative) | 0.447 (0.215–0.929) | 0.031 | 0.529 (0.284–0.987) | 0.045 |
PD-L1ICS* (Positive vs. Negative) | 0.387 (0.163–0.918) | 0.031 | 0.347 (0.158–0.760) | 0.008 |
PD-L1CPS* (Positive vs. Negative) | 0.345 (0.167–0.711) | 0.004 | 0.577 (0.306–1.088) | 0.089 |
Variables | OS1 | OS2 | DFS | |||
---|---|---|---|---|---|---|
HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | |
NSE(U/ml) (≤ 15.2 vs. > 15.2) | 1.838 (0.591–5-716) | 0.293 | 2.723 (0.683–10.859) | 0.156 | ||
FIGO* stage (I-II vs. III- IV) | 1.266 (0.418–3.832) | 0.677 | 0.688 (0.188–2.523) | 0.573 | ||
PD-L1CPS* (Positive vs. Negative) | 0.363 (0.139–0.950) | 0.039 | ||||
Parametrium invasion (No vs.Yes) | 1.215 (0.339–4.358) | 0.765 | 1.871 (0.516–6.787) | 0.341 | 2.791 (0.847–9.200) | 0.092 |
PNI* (No vs. Yes vs. Na) | 3.617 (1.361–9.616) | 0.010 | 5.615 (2.072–15.217) | 0.001 | 2.576 (1.135–5.847) | 0.024 |
PD-L1TPS* (Positive vs. Negative) | 0.569 (0.210–1.538) | 0.266 | 0.590 (0.266–1.309) | 0.194 | ||
PD-L1ICS* (Positive vs. Negative) | 0.199 (0.050–0.802) | 0.023 | 0.124 (0.036–0.425) | 0.001 | ||
Stromal invasion (< 1/2 vs. ≥ 1/2) | 2.417 (0.826–7.078) | 0.107 | ||||
LVSI* (No vs. Yes vs. Na) | 2.693 (0.638–11.376) | 0.178 | ||||
Postoperative therapy (No vs. Yes) | 0.148 (0.040–0.538) | 0.004 |