Deregulated Expression of IL-37 in Patients with Bladder Urothelial Cancer: The Diagnostic Potential of the IL-37e Isoform
Abstract
:1. Introduction
2. Results
2.1. IL-37 Levels Are Increased in BLCA versus Non-Cancerous Bladder Tissues
2.2. Increased IL-37 or SIGIRR Expression Are Favorable Prognostic Factors for OS in BLCA Patients
2.3. IL-37 and SIGIRR Levels Associated with Histopathological Parameters of BLCA Tumors
2.4. IL-37 and SIGIRR Gene Alterations Correlate with Altered Infiltration of the BLCA by Certain Immune Cell Subset Levels Associated with Histopathological Parameters of BLCA Tumors
2.5. IL-37 Expression Levels Correlate with Altered Infiltration of the BLCA by Certain Immune Cell Subsets
2.6. Human Bladder Cancer Cells Express IL-37b, c and e Isoforms
2.7. Human BLCA Biopsies Predominantly Express the IL-37e Isoform: Correlation with the Grade of the Tumor
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Assessment of IL-37 and SIGIRR Levels in BLCA versus Non-BLCA Lung Tissues
4.3. Analysis of Associations between IL-37 or SIGIRR Levels and Certain Pathological Characteristics of the BLCA Tumor
4.4. Exploration of Correlations between IL-37 and SIGIRR Gene Alterations or Expression Levels and Immune Cell Infiltration Patterns in BLCA Tumors
4.5. Human Bladder Cancer Biopsies
4.6. Cell Cultures
4.7. Extraction of Total RNA and Reverse Transcription
4.8. Quantitative Real Time PCR (qPCR)
4.9. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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IL-37 | SIGIRR | |||||||
---|---|---|---|---|---|---|---|---|
Non-BLCA vs. BLCA | ||||||||
n | Levels (Median; Range) | Fold Change | p-Value | n | Levels (Median; Range) | Fold Change | p-Value | |
Non-BLCA (normal) | 30 | 0 | 30 | 655.5 | ||||
BLCA | 411 | 2 | 2 | 1.44 × 10−10 | 411 | 691 | 1.05 | 3.82 × 10−1 |
Normal | 19 | 0 (0–0) | 19 | 23.11 (11.29–48.4) | ||||
Primary tumor | 408 | 0.09 (0–0.73) | 0.09 | NS | 408 | 29.31 (2.30–80.10) | 1.27 | 9.46 × 10−3 |
Tumors vs. adjacent normal | ||||||||
Adjacent normal | 19 | 0 | 19 | 507 | ||||
Tumor | 19 | 1 | 1 | 2.26 × 10−3 | 19 | 639 | 1.26 | 1.86 × 10−2 |
BLCA histological subtype | ||||||||
Normal | 19 | 0 (0–0) | 19 | 23.11 (11.29–48.4) | ||||
Papillary | 132 | 0.08 (0–0.91) | 0.08 | NS | 132 | 33.48 (4.25–82.13) | 1.45 | 2.88 × 10−2 |
Non-papillary | 271 | 0.09 (0–0.63) | 0.09 | 2.06 × 10−10 | 271 | 26.84 (2.30–75.22) | 1.16 | NS |
Cancer stage | ||||||||
Normal | 19 | 0 (0–0) | 19 | 23.11 (11.29–48.4) | ||||
Stage 1 | 2 | 1.03 (0–2.06) | 1.03 | NS | 2 | 40.08 (35.86–44.30) | 1.73 | NS |
Stage 2 | 129 | 0.1 (0–0.64) | 0.1 | 6.38 × 10−5 | 129 | 33.13 (3.81–84.25) | 1.43 | 9.77 × 10−4 |
Stage 3 | 137 | 0.08 (0–0.52) | 0.08 | 4.02 × 10−6 | 137 | 26.84 (2.30–70.21) | 1.16 | NS |
Stage 4 | 132 | 0.09 (0–0.73) | 0.09 | NS | 132 | 27.23 (4.33–78.70) | 1.18 | NS |
Nodal metastasis status | ||||||||
Normal | 19 | 0 (0–0) | 19 | 23.11 (11.29–48.4) | ||||
N0 | 237 | 0.09 (0–0.64) | 0.09 | 1.83 × 10−8 | 237 | 29.31 (2.30–71.13) | 1.27 | 1.45 × 10−2 |
N1 | 46 | 0.09 (0–0.4) | 0.09 | 1.82 × 10−4 | 46 | 26.85 (4.33–77.7) | 1.16 | NS |
N2 | 75 | 0.09 (0–1.05) | 0.09 | 1.62 × 10−7 | 75 | 27.16 (4.53–69.18) | 1.18 | NS |
N3 | 8 | 0.26 (0–0.95) | 0.26 | NS | 8 | 27.39 (5.29–59.47) | 1.19 | NS |
TP53 mutation status | ||||||||
Normal | 19 | 0 (0–0) | 19 | 23.11 (11.29–48.4) | ||||
Mutant | 193 | 0.116 (0–0.779) | 0.116 | 5.64 × 10−14 | 193 | 27.84 (2.3–84.45) | 1.20 | 2.45 × 10−2 |
Non-mutant | 215 | 0.069 (0–0616) | 0.069 | NS | 215 | 29.68 (3.67–71.13) | 1.28 | 6.38 × 10−3 |
ARID1A mutation status | ||||||||
Normal | 19 | 0 (0–0) | 19 | 23.11 (11.29–48.4) | ||||
Mutant | 76 | 0.096 (0–0.824) | 0.096 | 3.63 × 10−5 | 76 | 28.93 (2.3–70.52) | 1.25 | 1.80 × 10−2 |
Non-mutant | 324 | 0.091 (0–0.641) | 0.091 | NS | 324 | 29.69 (3.81–82.13) | 1.28 | 8.96 × 10−3 |
N | Median (Range) | Fold Change | p-Value | ||
---|---|---|---|---|---|
Total BLCA biopsies | |||||
Low-grade | 18 | 0.14 (0.007–25.18) | High- over low-grade: | 2.79 | 0.0269 |
High-grade | 49 | 0.39 (0.024–50.83) | |||
Grade 1 | 6 | 0.03 (0.007–1.88) | Grade 2 over Grade 1 | 11.67 | 0.049 |
Grade 2 | 16 | 0.35 (0.029–25.18) | Grade 3 over Grade 2 | 0.94 | NS |
Grade 3 | 45 | 0.33 (0.024–50.85) | Grade 3 over Grade 1 | 11.00 | 0.017 |
Non-muscle-invasive BLCA biopsies | |||||
Low-grade | 18 | 0.14 (0.007–25.18) | High- over low-grade: | 2.79 | 0.0269 |
High-grade | 16 | 0.39 (0.024–50.83) | |||
Grade 1 | 6 | 0.03 (0.007–1.88) | Grade 2 over Grade 1 | 11.67 | 0.049 |
Grade 2 | 16 | 0.34 (0.029–25.18) | Grade 3 over Grade 2 | 0.94 | NS |
Grade 3 | 12 | 0.35 (0.026–11.34) | Grade 3 over Grade 1 | 11.00 | NS |
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Papasavva, M.; Amvrosiou, S.; Pilala, K.-M.; Soureas, K.; Christodoulou, P.; Ji, Y.; Stravodimos, K.; Xu, D.; Scorilas, A.; Avgeris, M.; et al. Deregulated Expression of IL-37 in Patients with Bladder Urothelial Cancer: The Diagnostic Potential of the IL-37e Isoform. Int. J. Mol. Sci. 2023, 24, 9258. https://doi.org/10.3390/ijms24119258
Papasavva M, Amvrosiou S, Pilala K-M, Soureas K, Christodoulou P, Ji Y, Stravodimos K, Xu D, Scorilas A, Avgeris M, et al. Deregulated Expression of IL-37 in Patients with Bladder Urothelial Cancer: The Diagnostic Potential of the IL-37e Isoform. International Journal of Molecular Sciences. 2023; 24(11):9258. https://doi.org/10.3390/ijms24119258
Chicago/Turabian StylePapasavva, Maria, Styliana Amvrosiou, Katerina-Marina Pilala, Konstantinos Soureas, Panayiota Christodoulou, Yuan Ji, Konstantinos Stravodimos, Damo Xu, Andreas Scorilas, Margaritis Avgeris, and et al. 2023. "Deregulated Expression of IL-37 in Patients with Bladder Urothelial Cancer: The Diagnostic Potential of the IL-37e Isoform" International Journal of Molecular Sciences 24, no. 11: 9258. https://doi.org/10.3390/ijms24119258