CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Objectives
2.2. Patients and Tumor Samples
2.3. Immunohistochemistry
2.4. Evaluation of TILs
2.5. Statistical Analysis
3. Results
3.1. Correlations of CD11b, CD66b and CXCR2 Expression with Clinicopathological Features
3.2. Correlations between CD11b, CD66b and CXCR2 in TNBC Samples
3.3. Correlations of CD11b, CD66b and CXCR2 Expression with Immune Tumor Microenvironment
3.4. Survival Analyses
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AB | Antibody |
AR | Androgen receptor |
CAFs | Cancer associated fibroblasts |
CI | Confidence interval |
ECM | Extracellular matrix |
ER | Estrogen receptor |
FOXA1 | Forkhead box protein A1 |
HR | Hazard ratio |
IHC | Immunohistochemistry |
NK | Natural killer |
OS | Overall survival |
PR | Progesterone receptor |
ROI | Region of interest |
RFS | Relapse-free survival |
TIL | Tumor-infiltrating lymphocytes |
TMA | Tissue microarray |
TME | Tumor microenvironment |
TNBC | Triple-negative breast cancer |
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Patient Features | Number of Patients(n = 290) | % | |
---|---|---|---|
Age (years), median (min to max) | 57.72 | [28.54–89.10] | |
<55 | 129 | 44.5 | |
≥55 | 161 | 55.5 | |
Tumor size | |||
T1 | 134 | 46.2 | |
T2 | 138 | 47.6 | |
T3/T4 | 18 | 6.2 | |
Nodal status | |||
N− | 189 | 65.2 | |
N+ | 101 | 34.8 | |
Histological grade (4 missing values) | |||
1–2 | 66 | 23.1 | |
3 | 220 | 76.9 | |
Histology (3 missing values) | |||
Ductal | 238 | 82.9 | |
Lobular | 15 | 5.2 | |
Other (1) | 34 | 11.9 | |
Adjuvant chemotherapy (1 missing value) | |||
No | 71 | 24.6 | |
Yes | 218 | 75.4 | |
Basal-like phenotype (2 missing value) | |||
No | 101 | 35.1 | |
Yes (basal) | 187 | 64.9 | |
Molecular apocrine phenotype (17 missing values) | |||
No | 159 | 58.2 | |
Yes (molecular apocrine) | 114 | 41.8 | |
TIL %, median (6 missing values) | |||
<5% | 134 | 47.2 | |
≥5% | 150 | 52.8 | |
CD3+ cell density (2 missing values) | |||
Low | 144 | 50.0 | |
High | 144 | 50.0 | |
CD8+ cell density (6 missing values) | |||
Low | 142 | 50.0 | |
High | 142 | 50.0 | |
PD-L1TC (24 missing values) | |||
<1% | 119 | 44.7 | |
≥1% | 147 | 55.3 | |
PD-L1SC (27 missing values) | |||
0 | 48 | 18.3 | |
[0–10] | 85 | 32.3 | |
[10–50] | 72 | 27.4 | |
≥50 | 58 | 22.1 | |
PD-1SC (21 missing values) | |||
0 | 69 | 25.7 | |
[0–10] | 72 | 26.8 | |
[10–50] | 106 | 39.4 | |
≥50 | 22 | 8.2 | |
CD11b+ cell density (15 missing values) | |||
Low | 137 | 49.8 | |
High | 138 | 50.2 | |
CD66b+ cell density (14 missing values) | |||
Low | 138 | 50.0 | |
High | 138 | 50.0 | |
CXCR2+ cell density (3 missing values) | |||
Low | 144 | 50.2 | |
High | 143 | 49.8 |
Variables | CD11b | CD66b | CXCR2 | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Low | High | p-Value | Low | High | p-Value | Low | High | p-Value | ||||||||
N | % | N | % | N | % | N | % | N | % | N | % | |||||
Age (years) | ||||||||||||||||
<55 | 53 | 38.7 | 73 | 52.9 | 0.018 | 72 | 52.2 | 55 | 39.9 | 0.040 | 61 | 42.4 | 68 | 47.6 | 0.377 | |
≥55 | 84 | 61.3 | 65 | 47.1 | 66 | 47.8 | 83 | 60.1 | 83 | 57.6 | 75 | 52.5 | ||||
Tumor size | ||||||||||||||||
T1 | 56 | 40.9 | 71 | 51.5 | 0.079 | 70 | 50.7 | 57 | 41.3 | 0.116 | 68 | 47.2 | 64 | 44.8 | 0.675 | |
T2/T3/T4 | 81 | 59.1 | 67 | 48.6 | 68 | 49.3 | 81 | 58.7 | 76 | 52.8 | 79 | 55.2 | ||||
Nodal status | ||||||||||||||||
N− | 84 | 61.3 | 95 | 68.8 | 0.190 | 88 | 63.8 | 92 | 66.7 | 0.613 | 90 | 62.5 | 97 | 67.8 | 0.343 | |
N+ | 53 | 38.7 | 43 | 31.2 | 50 | 36.2 | 46 | 33.3 | 54 | 37.5 | 46 | 32.2 | ||||
Histological grade | ||||||||||||||||
1–2 | 48 | 35.8 | 14 | 10.2 | <0.001 | 47 | 34.8 | 14 | 10.2 | <0.001 | 49 | 34.8 | 16 | 11.3 | <0.001 | |
3 | 86 | 64.2 | 123 | 89.8 | 88 | 65.2 | 123 | 89.8 | 92 | 65.3 | 126 | 88.7 | ||||
Histology | ||||||||||||||||
Ductal | 109 | 79.6 | 118 | 87.4 | 0.082 | 109 | 79.6 | 120 | 88.2 | 0.051 | 111 | 78.2 | 124 | 87.3 | 0.041 | |
Other | 28 | 20.4 | 17 | 12.6 | 28 | 20.4 | 16 | 11.8 | 31 | 21.8 | 18 | 12.7 | ||||
Adjuvant chemotherapy | ||||||||||||||||
No | 40 | 29.4 | 26 | 18.8 | 0.041 | 25 | 18.3 | 42 | 30.4 | 0.019 | 38 | 26.6 | 32 | 22.4 | 0.409 | |
Yes | 96 | 70.6 | 112 | 81.2 | 112 | 81.8 | 96 | 69.6 | 105 | 73.4 | 111 | 77.6 | ||||
Basal-like phenotype | ||||||||||||||||
No | 55 | 40.4 | 41 | 29.9 | 0.069 | 46 | 33.8 | 52 | 37.7 | 0.505 | 56 | 39.4 | 45 | 31.5 | 0.160 | |
Yes (Basal) | 81 | 59.6 | 96 | 70.1 | 90 | 66.2 | 86 | 62.3 | 86 | 60.6 | 98 | 68.5 | ||||
Molecular apocrine phenotype | ||||||||||||||||
No | 61 | 48.4 | 91 | 68.4 | 0.001 | 71 | 55.9 | 83 | 61.5 | 0.359 | 66 | 50.0 | 93 | 66.4 | 0.006 | |
Yes (Molecular apocrine) | 65 | 51.6 | 42 | 31.6 | 56 | 44.1 | 52 | 38.5 | 66 | 50.0 | 47 | 33.6 |
Variables | CD11b Density | CD66b Density | CXCR2 Density | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Low | High | p-Value | Low | High | p-Value | Low | High | p-Value | ||||||||
N | % | N | % | N | % | N | % | N | % | N | % | |||||
TILs | ||||||||||||||||
<5% | 88 | 64.7 | 39 | 29.1 | <0.001 | 70 | 51.1 | 56 | 41.8 | 0.125 | 84 | 60.0 | 49 | 34.8 | <0.001 | |
≥5% | 48 | 35.3 | 95 | 70.9 | 67 | 48.9 | 78 | 58.2 | 56 | 40.0 | 92 | 65.3 | ||||
CD3+ density | ||||||||||||||||
Low | 94 | 69.1 | 42 | 30.4 | <0.001 | 73 | 52.9 | 63 | 45.7 | 0.229 | 91 | 63.6 | 52 | 36.4 | <0.001 | |
High | 42 | 30.9 | 96 | 69.6 | 65 | 47.1 | 75 | 54.4 | 52 | 36.4 | 91 | 63.6 | ||||
CD8+ density | ||||||||||||||||
Low | 78 | 58.2 | 57 | 41.6 | 0.006 | 77 | 56.2 | 57 | 41.9 | 0.018 | 90 | 63.8 | 51 | 36.2 | <0.001 | |
High | 56 | 41.8 | 80 | 58.4 | 60 | 43.8 | 79 | 58.1 | 51 | 36.2 | 90 | 63.8 | ||||
PD-L1TC | ||||||||||||||||
<1% | 68 | 56.7 | 45 | 33.8 | <0.001 | 59 | 48.0 | 52 | 39.4 | 0.168 | 72 | 56.7 | 47 | 34.1 | <0.001 | |
≥1% | 52 | 43.3 | 88 | 66.2 | 64 | 52.0 | 80 | 60.6 | 55 | 43.3 | 91 | 65.9 | ||||
PD-L1SC | ||||||||||||||||
<10% | 72 | 61.0 | 53 | 39.9 | 0.001 | 77 | 62.6 | 49 | 37.7 | <0.001 | 76 | 60.8 | 57 | 41.6 | 0.002 | |
≥10% | 46 | 39.0 | 80 | 60.2 | 46 | 37.4 | 81 | 62.3 | 49 | 39.2 | 80 | 58.4 | ||||
PD-1SC | ||||||||||||||||
<10% | 76 | 61.8 | 59 | 44.7 | 0.006 | 84 | 65.6 | 51 | 38.9 | <0.001 | 84 | 63.6 | 57 | 41.9 | <0.001 | |
≥10% | 47 | 38.2 | 73 | 55.3 | 44 | 34.4 | 80 | 61.1 | 48 | 36.4 | 79 | 58.1 |
Variable | OS | RFS | |||||
---|---|---|---|---|---|---|---|
HR | 95% CI | p-Value | HR | 95% CI | p-Value | ||
Age (years) | |||||||
<55 | 1 | 1 | |||||
≥55 | 2.07 | 1.31–3.27 | 0.001 | 1.43 | 0.89–2.31 | 0.137 | |
Tumor size | |||||||
T1 | 1 | 1 | |||||
T2/T3/T4 | 2.82 | 1.75–4.55 | <0.001 | 2.59 | 1.55–4.34 | <0.001 | |
Nodal status | |||||||
N− | 1 | 1 | |||||
N+ | 2.25 | 1.48–3.42 | <0.001 | 4.34 | 2.67–7.05 | <0.001 | |
Histological grade | |||||||
1–2 | 1 | 1 | |||||
3 | 0.79 | 0.50–1.26 | 0.328 | 1.02 | 0.59–1.76 | 0.931 | |
Histology | |||||||
Ductal | 1 | 1 | |||||
Other | 0.61 | 0.33–1.15 | 0.108 | 0.91 | 0.49–1.69 | 0.764 | |
Adjuvant chemotherapy | |||||||
No | 1 | 1 | |||||
Yes | 0.33 | 0.21–0.50 | <0.001 | 0.5 | 0.31–0.81 | 0.007 | |
Basal-like phenotype | |||||||
No | 1 | 1 | |||||
Yes (basal) | 1.06 | 0.68–1.66 | 0.787 | 0.85 | 0.53–1.36 | 0.495 | |
Molecular apocrine phenotype | |||||||
No | 1 | 1 | |||||
Yes (molecular apocrine) | 1.6 | 1.04–2.46 | 0.033 | 1.65 | 1.03–2.63 | 0.038 | |
TILs | |||||||
<5% | 1 | 1 | |||||
≥5% | 0.52 | 0.33–0.80 | 0.003 | 0.47 | 0.29–0.76 | 0.002 | |
CD3+ density | |||||||
Low | 1 | 1 | |||||
High | 0.72 | 0.47–1.10 | 0.126 | 0.64 | 0.40–1.02 | 0.059 | |
CD8+ density | |||||||
Low | 1 | 1 | |||||
High | 1.11 | 0.72–1.70 | 0.634 | 0.91 | 0.57–1.45 | 0.696 | |
PD-L1TC | |||||||
<1% | 1 | 1 | |||||
≥1% | 0.66 | 0.42–1.02 | 0.061 | 0.59 | 0.37–0.96 | 0.034 | |
PD-L1SC | |||||||
<10% | 1 | 1 | |||||
≥10% | 0.67 | 0.42–1.06 | 0.081 | 0.57 | 0.35–0.95 | 0.028 | |
PD-1SC | |||||||
<10% | 1 | 1 | |||||
≥10% | 1.09 | 0.71–1.67 | 0.708 | 0.92 | 0.57–1.47 | 0.725 | |
CD11b density | |||||||
Low | 1 | 1 | |||||
High | 0.72 | 0.46–1.12 | 0.141 | 0.66 | 0.40–1.07 | 0.088 | |
CD66b density | |||||||
Low | 1 | 1 | |||||
High | 1.29 | 0.83–2.01 | 0.251 | 1.2 | 0.74–1.93 | 0.456 | |
CXCR2 density | |||||||
Low | 1 | 1 | |||||
High | 0.61 | 0.40–0.95 | 0.026 | 0.52 | 0.32–0.85 | 0.007 |
Variables | OS | RFS | |||||
---|---|---|---|---|---|---|---|
HR | 95% CI | p-Value | HR | 95% CI | p-Value | ||
Tumor size | <0.001 | 0.017 | |||||
T1 | 1 | 1 | |||||
T2/T3/T4 | 2.48 | 1.49–4.13 | 1.87 | 1.10–3.17 | |||
Nodal status | <0.001 | <0.001 | |||||
N− | 1 | 1 | |||||
N+ | 2.51 | 1.59–3.97 | 4.28 | 2.57–7.12 | |||
Adjuvant chemotherapy | <0.001 | 0.002 | |||||
No | 1 | 1 | |||||
Yes | 0.32 | 0.20–0.50 | 0.43 | 0.26–0.71 | |||
Histology | 0.002 | ||||||
Ductal | 1 | ||||||
Other | 0.38 | 0.19–0.76 | |||||
TILs | 0.008 | 0.01 | |||||
<5% | 1 | 1 | |||||
≥5% | 0.54 | 0.34–0.86 | 0.52 | 0.31–0.86 | |||
CXCR2 | 0.05 | 0.058 | |||||
Low | 1 | 1 | |||||
High | 0.64 | 0.40–1.01 | 0.61 | 0.37–1.02 |
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Boissière-Michot, F.; Jacot, W.; Massol, O.; Mollevi, C.; Lazennec, G. CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers. Cancers 2021, 13, 2328. https://doi.org/10.3390/cancers13102328
Boissière-Michot F, Jacot W, Massol O, Mollevi C, Lazennec G. CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers. Cancers. 2021; 13(10):2328. https://doi.org/10.3390/cancers13102328
Chicago/Turabian StyleBoissière-Michot, Florence, William Jacot, Océane Massol, Caroline Mollevi, and Gwendal Lazennec. 2021. "CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers" Cancers 13, no. 10: 2328. https://doi.org/10.3390/cancers13102328