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Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer

Thomas, Anita, Slade, Kimberly Sue, Blaheta, Roman A., Markowitsch, Sascha D., Stenzel, Philipp, Tagscherer, Katrin E., Roth, Wilfried, Schindeldecker, Mario, Michaelis, Martin, Rothweiler, Florian, and others. (2022) Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer. Cancers, 14 (7). Article Number 1683. ISSN 2072-6694. (doi:10.3390/cancers14071683) (KAR id:95208)


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.

Item Type: Article
DOI/Identification number: 10.3390/cancers14071683
Uncontrolled keywords: penile cancer; squamous cell carcinoma; c-MET; resistant cell lines; marker; targeted therapy; tivantinib; cabozantinib
Subjects: R Medicine > RC Internal medicine > RC254 Neoplasms. Tumors. Oncology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Martin Michaelis
Date Deposited: 27 May 2022 16:15 UTC
Last Modified: 30 May 2022 08:37 UTC
Resource URI: (The current URI for this page, for reference purposes)

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