Anita Thomas, Kimberly Sue Slade, Roman A. Blaheta, Sascha Dennis Markowitsch, Philipp J. Stenzel, Katrin Tagscherer, Wilfried Roth, Mario Schindeldecker, Martin Michaelis, Florian Rothweiler, Jaroslav Cinatl, Robert Hans Dotzauer, Olesya Vakhrusheva, Maarten Albersen, Axel Haferkamp, Eva Jüngel, Jindrich Cinatl, Igor Tsaur
- Whereas the lack of biomarkers in penile cancer (PeCa) impedes the development of efficacious treatment protocols, preliminary evidence suggests that c-MET and associated signaling elements may be dysregulated in this disorder. In the following study, we investigated whether c-MET and associated key molecular elements may have prognostic and therapeutic utility in PeCa. Formalin-fixed, paraffin-embedded tumor tissue from therapy-naïve patients with invasive PeCa was used for tissue microarray (TMA) analysis. Immunohistochemical staining was performed to determine the expression of the proteins c-MET, PPARg, β-catenin, snail, survivin, and n-MYC. In total, 94 PeCa patients with available tumor tissue were included. The median age was 64.9 years. High-grade tumors were present in 23.4%, and high-risk HPV was detected in 25.5%. The median follow-up was 32.5 months. High expression of snail was associated with HPV-positive tumors. Expression of β-catenin was inversely associated with grading. In both univariate COX regression analysis and the log-rank test, an increased expression of PPARg and c-MET was predictive of inferior disease-specific survival (DSS). Moreover, in multivariate analysis, a higher expression of c-MET was independently associated with worse DSS. Blocking c-MET with cabozantinib and tivantinib induced a significant decrease in viability in the primary PeCa cell line UKF-PeC3 isolated from the tumor tissue as well as in cisplatin- and osimertinib-resistant sublines. Strikingly, a higher sensitivity to tivantinib could be detected in the latter, pointing to the promising option of utilizing this agent in the second-line treatment setting.
MetadatenAuthor: | Anita ThomasGND, Kimberly Sue Slade, Roman A. BlahetaORCiD, Sascha Dennis MarkowitschGND, Philipp J. StenzelORCiDGND, Katrin TagschererORCiDGND, Wilfried RothGND, Mario SchindeldeckerORCiDGND, Martin MichaelisORCiDGND, Florian RothweilerGND, Jaroslav Cinatl, Robert Hans DotzauerORCiDGND, Olesya Vakhrusheva, Maarten AlbersenORCiD, Axel HaferkampGND, Eva JüngelORCiDGND, Jindrich CinatlORCiDGND, Igor TsaurORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-831386 |
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DOI: | https://doi.org/10.3390/cancers14071683 |
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ISSN: | 2072-6694 |
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Parent Title (English): | Cancers |
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Publisher: | MDPI |
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Place of publication: | Basel |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2022/03/25 |
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Date of first Publication: | 2022/03/25 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2024/06/25 |
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Tag: | c-MET; cabozantinib; marker; penile cancer; resistant cell lines; squamous cell carcinoma; targeted therapy; tivantinib |
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Volume: | 14 |
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Issue: | 7, art. 1683 |
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Article Number: | 1683 |
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Page Number: | 15 |
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First Page: | 1 |
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Last Page: | 15 |
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Note: | Funding Information: This research was supported by the Werner Jackstädt-Stiftung-Foundation, Loercher-Foundation for Medical Research, European Urological Scholarship Programme (EUSP), and by the friendly society Hilfe für krebskranke Kinder Frankfurt e.V. and its foundation Frankfurter Stiftung für krebskranke Kinder. |
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HeBIS-PPN: | 522324444 |
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Institutes: | Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |
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