Franz Rödel, Daniel Martin, Christina Helmke, Panagiotis Balermpas, Emmanouil Fokas, Ulrike Wieland, Margret Rave-Fränk, Julia Kitz, Yves Matthess, Monika Raab, Klaus Strebhardt, Claus Rödel
- We have recently shown that caspase-8 is a new substrate of Polo-like kinase 3 (Plk3) that phosphorylates the protein on residue T273 thereby promoting its pro-apoptotic function. In the present study we aimed to investigate the clinical relevance of Plk3 expression and phosphorylation of caspase-8 at T273 in patients with anal squamous cell carcinoma (SSC) treated with 5-fluorouracil and mitomycin C-based chemoradiotherapy (CRT). Immunohistochemical detection of the markers was performed in pretreatment biopsy specimens of 95 patients and was correlated with clinical/histopathologic characteristics including HPV-16 virus load/p16INK4a expression and cumulative incidence of local and distant failure, cancer specific survival (CSS), and overall survival (OS). We observed significant positive correlations between Plk3 expression, pT273 caspase-8 signal, and levels of HPV-16 virus DNA load/p16INK4a detection. Patients with high scores of Plk3 and pT273 caspase-8 showed increased local control (p = 0.011; p = 0.001), increased CSS (p = 0.011; p = 0.013) and OS (p = 0.024; p = 0.001), while the levels of pT273 caspase-8 were significantly associated (p = 0.033) with distant metastases. In multivariate analyses Plk3 expression remained significant for local failure (p = 0.018), CSS (p = 0.016) and OS (p = 0.023). Moreover, a combined HPV16 DNA load and Plk3 or pT273 caspase-8 variable revealed a significant correlation to decreased local failure (p = 0.001; p = 0.009), increased CSS (p = 0.016; p = 0.023) and OS (p = 0.003; p = 0.003). In conclusion these data indicate that elevated levels of Plk3 and pT273 caspase-8 are correlated with favorable clinical outcome in patients with anal SCC treated with concomitant CRT.
MetadatenAuthor: | Franz RödelORCiDGND, Daniel MartinORCiD, Christina Helmke, Panagiotis BalermpasORCiDGND, Emmanouil FokasORCiDGND, Ulrike Wieland, Margret Rave-Fränk, Julia Kitz, Yves MatthessORCiDGND, Monika RaabORCiD, Klaus StrebhardtORCiDGND, Claus RödelORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-456252 |
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DOI: | https://doi.org/10.18632/oncotarget.10801 |
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ISSN: | 1949-2553 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/27462786 |
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Parent Title (English): | OncoTarget |
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Publisher: | Impact Journals LLC |
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Place of publication: | [s. l.] |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2016 |
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Date of first Publication: | 2016/07/23 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2018/02/06 |
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Tag: | Polo-like kinase 3; anal carcinoma; caspase-8; chemoradiotherapy; local control |
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Volume: | 7 |
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Issue: | 33 |
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Page Number: | 11 |
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First Page: | 53339 |
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Last Page: | 53349 |
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Note: | All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. |
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HeBIS-PPN: | 426623479 |
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Institutes: | Biowissenschaften / Biowissenschaften |
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| Medizin / 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 - Namensnennung 3.0 |
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