Interleukin-1β/Interleukin (IL)-1-Receptor-Antagonist (IL1-RA) Axis in Invasive Bladder Cancer—An Exploratory Analysis of Clinical and Tumor Biological Significance
Abstract
:1. Introduction
2. Results
2.1. Patients’ Characteristics
2.2. Expression Characteristics of IL-1β and IL1RA
2.3. Correlation of IL-1 Axis with Histopathologic Parameters
2.4. Combined Scores and Clinical Data
2.5. Correlation of IL-1 Axis with Ki-67 and AKT Expression
2.6. Survival Analysis
2.7. Uni- and Multivariate Cox Proportional Hazard Analysis
3. Discussion
4. Materials and Methods
4.1. Patient Cohorts
4.2. Tissue Microarray (TMA) and Immunohistochemical (IHC) Staining
4.3. Immunohistochemical Protocol
4.4. Patient Follow-up
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient Characteristics | Group I (n = 102) | Group II (n = 92) | p | ||
---|---|---|---|---|---|
N | % | n | % | ||
Gender | 0.56 | ||||
-Female | 24 | 23.53 | 25 | 27.18 | |
-Male | 78 | 76.47 | 67 | 72.82 | |
Age | Median 69 | Range (59–74) | Median 65 | Range (55–72) | 0.19 |
Pathological stage | 0.55 | ||||
-T1 | 0 | 0.00 | 9 | 9.78 | |
-T2 | 31 | 30.39 | 21 | 22.82 | |
-T3 | 47 | 46.08 | 42 | 45.66 | |
-T4 | 24 | 23.53 | 18 | 19.57 | |
-Only CIS | 0 | 0.00 | 2 | 2.17 | |
Lymph node status | 0.50 | ||||
-N0 | 58 | 56.86 | 57 | 61.95 | |
-N+ | 44 | 43.14 | 35 | 38.05 | |
Distant metastasis | 0.59 | ||||
-M0 | 89 | 87.23 | 82 | 89.13 | |
-M1 | 9 | 8.83 | 10 | 10.87 | |
-Mx | 4 | 3.93 | 0 | 0.00 | |
Pathological grade | 0.94 | ||||
-G1 | 0 | 0.00 | 1 | 1.08 | |
-G2 | 24 | 23.53 | 20 | 21.74 | |
-G3 | 78 | 76.47 | 71 | 77.18 | |
Resection margin status | 0.74 | ||||
-R0 | 84 | 82.35 | 74 | 80.43 | |
-R1 | 15 | 14.70 | 14 | 15.22 | |
-R2 | 3 | 2.95 | 2 | 2.18 | |
-Rx | 0 | 0.00 | 2 | 2.17 | |
Carcinoma in situ (CIS) | 0.57 | ||||
-No | 68 | 66.66 | 61 | 66.31 | |
-Yes | 29 | 28.44 | 31 | 33.69 | |
-CISx | 5 | 4.90 | 0 | 0.00 |
Histopathology Variables | IL-1β Expression (H-Score) | IL-1RA Expression (H-Score) | IL1-β/IL-1RA Ratio (Cut-Off 0.7) |
---|---|---|---|
Tumor grade | Medians | ||
G2 | 188 | 250 *** | 0.7 |
G3 | 193 * | 185 | 1.1 *** |
Tumor stadium pT | |||
T2 | 205 | 178 | 1.0 |
T3 | 190 | 200 | 1.0 |
T4 | 190 | 200 | 0.9 |
Lymphatic invasion | |||
No | 180 | 194 | 1.0 |
yes | 210 * | 200 | 1.0 |
Vascular invasion | |||
no | 183 | 190 | 1.0 |
yes | 210 * | 203 | 1.0 |
Nodal invasion | |||
N0 | 185 | 194 | 1.0 |
N1 | 185 | 200 | 0.9 |
N2 | 210 | 205 | 1.1 |
N3 | 198 | 175 | 1.0 |
Metastatic disease | |||
M0 | 185 | 194 | 1.0 |
M1 | 210 | 200 | 1.0 |
Variable | Ki-67+ and IL-1β+ | Ki-67+ (15%) or IL-1β+ | Ki-67+ and IL1RA+ | Ki-67+ (15%) or IL-1RA+ |
---|---|---|---|---|
Pathological stage >T2 vs. T2 | 0.61 | 0.67 | 0.81 | 0.06 |
Nodal status N+ vs. N0 | 0.97 | 0.25 | 0.39 | 0.54 |
Metastasis status M+ vs. M0 | 0.28 | 0.40 | 0.46 | 0.56 |
Grade ≥G3 vs. <G3 | 1.00 | 0.02 | 0.52 | 0.57 |
Lymphatic invasion L+ vs. L0 | 0.93 | 0.51 | 0.30 | 0.70 |
Vascular invasion V+ vs. V0 | 0.02 | 0.92 | 0.33 | 0.90 |
Variable | Univariate Analysis | Multivariate Analysis | ||||
---|---|---|---|---|---|---|
Recurrence (RFS) | p | HR | 95% CI | p | HR | 95% CI |
Pathological stage >T2 vs. T2 | 0.0099 | 3.25 | 1.33–7.95 | 0.1339 | 2.14 | 0.79–5.80 |
Nodal status N+ vs. N0 | 0.0879 | 1.88 | 0.91–3.88 | - | ||
Metastasis status M+ vs. M0 | - | - | ||||
Grade ≥G3 vs. <G3 | 0.0531 | 1.30 | 0.60–2.83 | - | ||
IL-1β Low vs. high tumor expression (cut-off 160) | 0.0172 | 3.16 | 1.23–8.16 | 0.0265 | 2.97 | 1.14–7.77 |
Age, year | 0.2397 | 1.02 | 0.99–1.06 | - | ||
Variable | Univariate analysis | Multivariate analysis | ||||
CSS | p | HR | 95% CI | p | HR | 95% CI |
Pathological stage >T2 vs. T2 | 0.0107 | 2.53 | 1.24–5.17 | 0.3407 | 1.51 | 0.65–3.49 |
Nodal status N+ vs. N0 | 0.0309 | 1.96 | 1.06–3.62 | 0.3170 | 1.48 | 0.69–3.17 |
Metastasis status M+ vs. M0 | 0.0015 | 3.56 | 1.63–7.79 | 0.0504 | 2.58 | 1.00–6.65 |
Grade ≥G3 vs. <G3 | 0.0069 | 3.62 | 1.42–9.22 | 0.1247 | 2.38 | 0.79–7.18 |
IL-1β Low vs. high tumor expression (cut-off 160) | 0.0343 | 2.27 | 1.06–4.84 | 0.0460 | 2.35 | 1.02–5.42 |
Age, year | 0.0047 | 1.05 | 1.01–1.08 | 0.3421 | 1.02 | 0.98–1.06 |
Variable | Univariate analysis | Multivariate analysis | ||||
OS | p | HR | 95% CI | p | HR | 95% CI |
Pathological stage >T2 vs. T2 | 0.0020 | 2.79 | 1.45–5.33 | 0.1240 | 1.85 | 0.85–4.03 |
Nodal status N+ vs. N0 | 0.0258 | 1.85 | 1.08–3.17 | 0.1909 | 1.60 | 0.79–3.24 |
Metastasis status M+ vs. M0 | 0.0036 | 3.13 | 1.45–6.73 | 0.1148 | 2.12 | 0.83–5.37 |
Grade ≥G3 vs. < G3 | 0.0173 | 2.31 | 1.16–4.60 | 0.1611 | 1.94 | 0.77–4.88 |
IL-1β Low vs. high tumor expression (cut-off 160) | 0.0082 | 2.54 | 1.27–5.06 | 0.0249 | 2.40 | 1.12–5.18 |
Age, year | 0.0031 | 1.05 | 1.02–1.08 | 0.1274 | 1.03 | 0.99–1.07 |
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Vukovic, M.; Chamlati, J.M.; Hennenlotter, J.; Todenhöfer, T.; Lütfrenk, T.; Jersinovic, S.; Tsaur, I.; Stenzl, A.; Rausch, S. Interleukin-1β/Interleukin (IL)-1-Receptor-Antagonist (IL1-RA) Axis in Invasive Bladder Cancer—An Exploratory Analysis of Clinical and Tumor Biological Significance. Int. J. Mol. Sci. 2024, 25, 2447. https://doi.org/10.3390/ijms25042447
Vukovic M, Chamlati JM, Hennenlotter J, Todenhöfer T, Lütfrenk T, Jersinovic S, Tsaur I, Stenzl A, Rausch S. Interleukin-1β/Interleukin (IL)-1-Receptor-Antagonist (IL1-RA) Axis in Invasive Bladder Cancer—An Exploratory Analysis of Clinical and Tumor Biological Significance. International Journal of Molecular Sciences. 2024; 25(4):2447. https://doi.org/10.3390/ijms25042447
Chicago/Turabian StyleVukovic, Marko, Jorge M. Chamlati, Jörg Hennenlotter, Tilman Todenhöfer, Thomas Lütfrenk, Sebastian Jersinovic, Igor Tsaur, Arnulf Stenzl, and Steffen Rausch. 2024. "Interleukin-1β/Interleukin (IL)-1-Receptor-Antagonist (IL1-RA) Axis in Invasive Bladder Cancer—An Exploratory Analysis of Clinical and Tumor Biological Significance" International Journal of Molecular Sciences 25, no. 4: 2447. https://doi.org/10.3390/ijms25042447
APA StyleVukovic, M., Chamlati, J. M., Hennenlotter, J., Todenhöfer, T., Lütfrenk, T., Jersinovic, S., Tsaur, I., Stenzl, A., & Rausch, S. (2024). Interleukin-1β/Interleukin (IL)-1-Receptor-Antagonist (IL1-RA) Axis in Invasive Bladder Cancer—An Exploratory Analysis of Clinical and Tumor Biological Significance. International Journal of Molecular Sciences, 25(4), 2447. https://doi.org/10.3390/ijms25042447