Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Cohort
2.2. Tissue Microarray Construction and Immunohistochemical Staining
2.3. Cell Culture and Induction of Drug Resistance
2.4. Drugs
2.5. Tumor Cell Growth
2.6. SDS-PAGE/Western Blot
2.7. Statistics
3. Results
3.1. Clinicopathological Features of Patients
3.2. Expression of Protein Candidates in the Tumor Tissue
3.3. Biomarker Correlations
3.4. Follow-Up
3.5. Induction of Resistance to Cisplatin and Osimertinib
3.6. Expression of Protein Candidates in Cell Lines
3.7. Modulation of Tumor Cell Growth by c-MET Inhibition
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Total Cohort (n = 94) | |
---|---|
Age at diagnosis | |
Mean (SD) | 64.9 (11.8) |
Median [Min, Max] | 67.0 [31.0, 90.0] |
≤65 | 45 (47.9%) |
>65 | 49 (52.1%) |
Primary surgery | |
Circumcision | 8 (8.5%) |
Tumor excision | 5 (5.3%) |
Partial penectomy | 55 (58.5%) |
Total penectomy | 25 (26.6%) |
Missing | 1 (1.1%) |
Tumor grade | |
Low (G1/G2) | 70 (74.5%) |
High (G3/G4) | 22 (23.4%) |
Missing | 2 (2.1%) |
pT stage | |
pT1 | 36 (38.3%) |
pT2 | 30 (31.9%) |
pT3 | 24 (25.5%) |
Missing | 4 (4.3%) |
HPV status | |
Negative | 65 (69.1%) |
Positive | 24 (25.5%) |
Missing | 5 (5.3%) |
pN stage | |
NX-0 | 77 (81.9%) |
N1 | 4 (4.3%) |
N2 | 8 (8.5%) |
N3 | 5 (5.3%) |
Recurrence status | |
No | 66 (70.2%) |
Yes | 28 (29.8%) |
Recurrence site | |
None | 66 (70.2%) |
Local | 18 (19.2%) |
Systemic | 10 (10.6%) |
Adjuvant therapy | |
None | 68 (72.3%) |
CTX | 16 (17.0%) |
Radiation | 1 (1.1%) |
CTX and Radiation | 2 (2.1%) |
Missing | 7 (7.4%) |
Tumor-dependent death | |
No | 61 (64.9%) |
Yes | 12 (12.8%) |
Missing | 21 (22.3%) |
Characteristic | OS | RFS | DSS | |||
---|---|---|---|---|---|---|
HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | |
PPARg | ||||||
Low expression | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |||
High expression | 2.77 (0.74–10.36) | 0.10 | 1.59 (0.41–6.13) | 0.50 | 5.18 (0.95–28.32) | 0.06 |
β-catenin | ||||||
Low expression | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |||
High expression | 0.76 (0.30–1.89) | 0.60 | 1.34 (0.52–3.40) | 0.50 | 0.74 (0.16–3.42) | 0.70 |
c-MET | ||||||
Low expression | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |||
High expression | 1.38 (0.57–3.37) | 0.50 | 1.05 (0.38–2.92) | 0.90 | 5.03 (1.08 -23.32) | 0.04 |
Grading | ||||||
low (G1/G2) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |||
high (G1/G2) | 1.72 (0.72–4.10) | 0.20 | 1.45 (0.48–4.32) | 0.50 | 0.40 (0.08–2.13) | 0.28 |
T-Stage | ||||||
pT1/pT2 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |||
pT3 | 0.89 (0.34–2.33) | 0.80 | 0.73 (0.27–1.97) | 0.50 | 0.56 (0.11–2.85) | 0.48 |
N-Stage | ||||||
N0 | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |||
N1/N2/N3 | 1.84 (0.67–5.04) | 0.20 | 1.11 (0.33–3.80) | 0.90 | 14.09 (3.29–60.43) | <0.001 |
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Thomas, A.; Slade, K.S.; Blaheta, R.A.; Markowitsch, S.D.; Stenzel, P.; Tagscherer, K.E.; Roth, W.; Schindeldecker, M.; Michaelis, M.; Rothweiler, F.; et al. Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer. Cancers 2022, 14, 1683. https://doi.org/10.3390/cancers14071683
Thomas A, Slade KS, Blaheta RA, Markowitsch SD, Stenzel P, Tagscherer KE, Roth W, Schindeldecker M, Michaelis M, Rothweiler F, et al. Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer. Cancers. 2022; 14(7):1683. https://doi.org/10.3390/cancers14071683
Chicago/Turabian StyleThomas, Anita, Kimberly Sue Slade, Roman A. Blaheta, Sascha D. Markowitsch, Philipp Stenzel, Katrin E. Tagscherer, Wilfried Roth, Mario Schindeldecker, Martin Michaelis, Florian Rothweiler, and et al. 2022. "Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer" Cancers 14, no. 7: 1683. https://doi.org/10.3390/cancers14071683