Prognostic Value of CXCR2 in Breast Cancer
Abstract
:1. Introduction
2. Results
2.1. Validation of the Detection of CXCR2 Expression
2.2. Analysis of CXCR2, CD66b and CD11b with Clinical Parameters of Breast Tumors
2.3. Analysis of the Correlation of CXCR2, CD11b and CD66b with Immune Infiltration of Tumors
2.4. CXCR2 Levels Are Correlated to AP-1 Levels
2.5. High CXCR2 Expression Is an Independent Prognostic Factor of Time to Relapse (TTR)
3. Discussion
4. Materials and Methods
4.1. Patients and Tumor Samples
4.2. Ethics Approval and Consent to Participate
4.3. Immunohistochemistry
4.4. In Situ Hybridization
4.5. Immunofluorescence
4.6. Transfection of Human CXCR2 in HEK-293 Cells
4.7. Protein Extraction and Western Blot
4.8. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
Ab | antibody |
CI | Confidence interval |
ER | Estrogen Receptor |
Her2 | Human Epidermal Growth Factor Receptor-2 |
HR | hormone receptor |
HdR | hazard ratio |
IF | immunofluorescence |
IHC | Immunohistochemistry |
ISH | in situ hybridization |
PR | Progesterone Receptor |
ROI | Region of interest |
SBR | Scarff–Bloom–Richardson |
TNBC | Triple-Negative Breast Cancer |
TTR | Time To Relapse |
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Variables | N | % |
---|---|---|
Age | ||
≤50 years | 36 | 34.3 |
50–65 years | 31 | 29.5 |
>65 years | 38 | 36.2 |
Type | ||
Ductal carcinoma | 77 | 73.3 |
Others | 28 | 26.7 |
SBR Grade | ||
I/II | 73 | 69.5 |
III | 32 | 30.5 |
pT | ||
pT1 | 42 | 40.4 |
pT2/pT3/pT4 | 62 | 59.6 |
Missing | 1 | / |
pN | ||
pN0 | 50 | 50 |
pN1/pN2/pN3 | 50 | 50 |
Missing | 5 | / |
pM | ||
pM0 | 80 | 76.2 |
pM1 | 1 | 1 |
pMX | 24 | 22.9 |
ER | ||
Negative | 36 | 34.3 |
Positive | 69 | 65.7 |
PR | ||
Negative | 52 | 49.5 |
Positive | 53 | 50.5 |
HR (if ER+ and/or PR+) | ||
Negative | 29 | 27.6 |
Positive | 76 | 72.4 |
Her2 | ||
Negative | 94 | 89.5 |
Positive | 11 | 10.5 |
Immunophenotype | ||
ER/PR− Her2− | 23 | 21.9 |
ER/PR± Her2+ | 11 | 10.5 |
ER/PR+ Her2− | 71 | 67.6 |
CD3 | ||
Negative | 54 | 51.4 |
Positive | 51 | 48.6 |
CD20 | ||
Negative | 74 | 70.5 |
Positive | 31 | 29.5 |
CD68 | ||
Negative | 5 | 4.8 |
Positive | 100 | 95.2 |
AP-1 | ||
Negative | 34 | 33 |
Positive | 69 | 67 |
Missing | 2 | / |
NF-KB | ||
Negative | 29 | 28.2 |
Positive | 74 | 71.8 |
Missing | 2 | / |
Variables | CXCR2 | CD11b | CD66b | ||||||
---|---|---|---|---|---|---|---|---|---|
N | Median (Range) | p-Value | N | Median (Range) | p-Value | N | Median (Range) | p-Value | |
Breast | |||||||||
Normal | 21 | 145.83 (24.20:714.60) | 0.026 | 21 | 242.90 (48.96:1014.74) | 0.001 | 21 | 85.46 (25.43:375.67) | 0.587 |
Cancer | 95 | 269.07 (19.38:4539.93) | 100 | 97.60 (0.71:85,867.80) | 98 | 68.96 (0.00:1920.86) |
Variables | CXCR2 | CD11b | CD66b | ||||||
---|---|---|---|---|---|---|---|---|---|
N | Median (Range) | p-Value | N | Median (Range) | p-Value | N | Median (Range) | p-Value | |
Age | |||||||||
≤50 years | 35 | 344.81 (31.4:7789.8) | 0.546 | 35 | 125.65 (4.7:13376.5) | 0.142 | 35 | 48.37 (4.4:10032.0) | 0.345 |
50–65 years | 31 | 268.28 (40.6:5085.6) | 31 | 79.02 (2.8:2963.4) | 30 | 52.17 (0.0:4842.6) | |||
>65 years | 34 | 406.60 (38.6:2201.2) | 36 | 146.6 (12.2:1118.5) | 37 | 90.0 (4.3:1501.9) | |||
Type | |||||||||
Ductal carcinoma | 73 | 351.60 (31.45:7789.79) | 0.468 | 75 | 146.54 (2.81:13376.50) | 0.357 | 76 | 70.36 (0.00:4842.61) | 0.355 |
Others | 27 | 295.24 (38.59:4998.79) | 27 | 79.02 (11.99:2579.57) | 26 | 35.29 (0.00:10031.97) | |||
SBR Grade | |||||||||
I/II | 69 | 298.45 (31.45:5085.62) | 0.002 | 71 | 111.87 (2.81:4568.04) | 0.032 | 71 | 36.08 (0.00:4842.61) | 0.038 |
III | 31 | 698.38 (55.23:7789.79) | 31 | 239.05 (9.36:13376.50) | 31 | 89.98 (5.45:10031.97) | |||
pT | |||||||||
pT1 | 41 | 263.28 (31.45:4998.79) | 0.102 | 42 | 90.11 (4.69:5192.38) | 0.051 | 42 | 48.56 (0.00:10031.97) | 0.119 |
pT2/pT3/pT4 | 58 | 379.24 (40.61:7789.79) | 59 | 200.09 (2.81:13376.50) | 59 | 85.58 (0.00:4842.61) | |||
pN | |||||||||
pN0 | 49 | 384.97 (31.45:7789.79) | 0.561 | 49 | 151.44 (4.69:13376.50) | 0.391 | 48 | 50.24 (4.41:10031.97) | 0.971 |
pN1/pN2/pN3 | 46 | 320.31 (38.59:3706.72) | 48 | 125.30 (2.81:9547.40) | 49 | 48.37 (0.00:1501.86) | |||
ER | |||||||||
Negative | 34 | 540.59 (83.49:7789.79) | 0.005 | 35 | 373.09 (11.99:13376.50) | <0.001 | 35 | 79.85 (0.00:10031.97) | 0.065 |
Positive | 66 | 296.85 (31.45:5085.62) | 67 | 85.91 (2.81:4568.04) | 67 | 34.50 (0.00:4842.61) | |||
PR | |||||||||
Negative | 51 | 472.48 (38.59:7789.79) | 0.002 | 51 | 262.77 (11.99:13376.50) | <0.001 | 51 | 75.46 (0.00:10031.97) | 0.08 |
Positive | 49 | 250.94 (31.45:2025.37) | 51 | 78.25 (2.81:4568.04) | 51 | 32.98 (0.00:1501.86) | |||
Her2 | |||||||||
Negative | 90 | 343.64 (31.45:7789.79) | 0.37 | 92 | 146.08 (2.81:13376.50) | 0.84 | 92 | 53.00 (0.00:10031.97) | 0.653 |
Positive | 10 | 285.67 (141.87:1067.14) | 10 | 103.49 (16.43:515.78) | 10 | 52.12 (5.45:570.98) | |||
Immunophenotype | |||||||||
ER/PR− Her2− | 23 | 1082.20 (154.6:7789.8) | <0.001 | 23 | 555.08 (12.0:13376.5) | <0.001 | 23 | 108.13 (6.4:10032.0) | 0.043 |
ER/PR± Her2+ | 10 | 285.67 (141.9:1067.1) | 10 | 103.49 (16.4:515.8) | 10 | 52.12 (5.5:571.0) | |||
ER/PR+ Her2− | 67 | 295.2 (31.4:5085.6) | 69 | 85.9 (2.8:4568.0) | 69 | 34.5 (0.0:4842.6) |
Variables | CXCR2 | CD11b | CD66b | ||||||
---|---|---|---|---|---|---|---|---|---|
N | Median (Range) | p-Value | N | Median (Range) | p-Value | N | Median (Range) | p-Value | |
CD3 | |||||||||
Negative | 52 | 253.21 (31.45:5085.62) | 53 | 85.91 (2.81:5192.38) | 0.013 | 52 | 48.44 (0.00:4842.61) | 0.828 | |
Positive | 48 | 490.63 (55.23:7789.79) | <0.001 | 49 | 205.85 (14.95:13376.50) | 50 | 60.56 (0.00:10031.97) | ||
CD20 | |||||||||
Negative | 70 | 292.12 (31.45:7789.79) | 0.007 | 71 | 98.49 (2.81:13376.50) | 0.003 | 71 | 48.37 (0.00:4842.61) | 0.608 |
Positive | 30 | 481.76 (156.36:4998.79) | 31 | 291.71 (19.02:9547.40) | 31 | 75.46 (6.41:10031.97) | |||
CD68 | |||||||||
Negative | 5 | 151.78 (31.45:725.11) | 0.053 | 5 | 41.97 (4.69:151.44) | 0.033 | 4 | 19.96 (4.41:159.43) | 0.196 |
Positive | 95 | 344.81 (38.59:7789.79) | 97 | 146.54 (2.81:13376.50) | 98 | 55.73 (0.00:10031.97) | |||
AP-1 | |||||||||
Negative | 31 | 268.59 (38.59:2201.23) | 0.05 | 32 | 88.07 (9.36:4568.04) | 0.079 | 32 | 32.40 (4.34:1416.34) | 0.311 |
Positive | 67 | 384.97 (31.45:7789.79) | 68 | 178.18 (2.81:13376.50) | 68 | 77.65 (0.00:10031.97) | |||
NF-kB | |||||||||
Negative | 29 | 288.99 (55.23:5085.62) | 0.516 | 29 | 124.96 (9.36:9547.40) | 0.64 | 28 | 42.22 (0.00:10031.97) | 0.857 |
Positive | 69 | 362.21 (31.45:7789.79) | 71 | 146.54 (2.81:13376.50) | 72 | 53.00 (0.00:2748.86) |
Parameter | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|
HdR (95% CI) | p-Value | HdR (95% CI) | p-Value | |
SBR Grade | ||||
I/II | 1.000 | 1.000 | ||
III | 1.117 (0.465–2.685) | 0.805 | 1.143 (0.382–3.420) | 0.811 |
Immune Type | ||||
ER/PR− Her2− | 1.000 | 1.000 | ||
ER/PR± Her2+ | 2.629 (0.749–9.233) | 0.131 | 1.718 (0.311–9.498) | 0.535 |
ER/PR+ Her2− | 1.038 (0.358–3.006) | 0.945 | 0.553 (0.137–2.237) | 0.406 |
Age at Diagnosis | ||||
<50 | 1.000 | 1.000 | ||
50–65 | 0.835 (0.317–2.200) | 0.714 | 0.641 (0.215–1.910) | 0.425 |
>65 | 0.682 (0.230–2.020) | 0.490 | 0.537 (0.161–1.789) | 0.311 |
CD20 | ||||
Negative | 1.000 | 1.000 | ||
Positive | 0.356 (0.119–1.065) | 0.065 | 0.252 (0.068–0.932) | 0.039 |
AP-1 | ||||
Negative | 1.000 | 1.000 | ||
Positive | 2.270 (0.761–6.773) | 0.142 | 3.404 (0.988–11.723) | 0.052 |
pT | ||||
T1 | 1.000 | 1.000 | ||
T2/T3/T4 | 1.727 (0.704–4.238) | 0.233 | 2.486 (0.909–6.797) | 0.076 |
CXCR2 invasive | ||||
low | 1.000 | 1.000 | ||
medium | 0.231 (0.073–0.731) | 0.013 | 0.168 (0.043–0.650) | 0.010 |
high | 0.277 (0.100–0.771) | 0.014 | 0.215 (0.054–0.840) | 0.028 |
CD11b invasive | ||||
low | 1.000 | |||
medium | 1.318 (0.457–3.803) | 0.610 | ||
high | 0.997 (0.342–2.906) | 0.995 | ||
CD66b invasive | ||||
low | 1.000 | |||
medium | 1.626 (0.584–4.529) | 0.352 | ||
high | 0.874 (0.278–2.749) | 0.818 |
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Boissière-Michot, F.; Jacot, W.; Fraisse, J.; Gourgou, S.; Timaxian, C.; Lazennec, G. Prognostic Value of CXCR2 in Breast Cancer. Cancers 2020, 12, 2076. https://doi.org/10.3390/cancers12082076
Boissière-Michot F, Jacot W, Fraisse J, Gourgou S, Timaxian C, Lazennec G. Prognostic Value of CXCR2 in Breast Cancer. Cancers. 2020; 12(8):2076. https://doi.org/10.3390/cancers12082076
Chicago/Turabian StyleBoissière-Michot, Florence, William Jacot, Julien Fraisse, Sophie Gourgou, Colin Timaxian, and Gwendal Lazennec. 2020. "Prognostic Value of CXCR2 in Breast Cancer" Cancers 12, no. 8: 2076. https://doi.org/10.3390/cancers12082076
APA StyleBoissière-Michot, F., Jacot, W., Fraisse, J., Gourgou, S., Timaxian, C., & Lazennec, G. (2020). Prognostic Value of CXCR2 in Breast Cancer. Cancers, 12(8), 2076. https://doi.org/10.3390/cancers12082076