Walter, R. F. H., Mairinger, F. D., Ting, S., Vollbrecht, C., Mairinger, T., Theegarten, D., Christoph, D. C., Schmid, K. W. and Wohlschlaeger, J. (2015). MDM2 is an important prognostic and predictive factor for platin-pemetrexed therapy in malignant pleural mesotheliomas and deregulation of P14/ARF (encoded by CDKN2A) seems to contribute to an MDM2-driven inactivation of P53. Br. J. Cancer, 112 (5). S. 883 - 891. LONDON: NATURE PUBLISHING GROUP. ISSN 1532-1827
Full text not available from this repository.Abstract
Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumour that is first-line treated with a combination of cisplatin and pemetrexed. Until now, predictive and prognostic biomarkers are lacking, making it a non-tailored therapy regimen with unknown outcome. P53 is frequently inactivated in MPM, but mutations are extremely rare. MDM2 and P14/ARF are upstream regulators of P53 that may contribute to P53 inactivation. Methods: A total of 72 MPM patients were investigated. MDM2 immunoexpression was assessed in 65 patients. MDM2 and P14/ARF mRNA expression was analysed in 48 patients of the overall collective. The expression results were correlated to overall survival (OS) and progression-free survival (PFS). Results: OS and PFS correlated highly significantly with MDM2 mRNA and protein expression, showing a dismal prognosis for patients with elevated MDM2 expression (for OS: Score (logrank) test: P <= 0.002, and for PFS: Score (logrank) test; P<0.007). MDM2 was identified as robust prognostic and predictive biomarker for MPM on the mRNA and protein level. P14/ARF mRNA expression reached no statistical significance, but Kaplan-Meier curves distinguished patients with low P14/ARF expression and hence shorter survival from patients with higher expression and prolonged survival. Conclusions: MDM2 is a prognostic and predictive marker for a platin-pemetrexed therapy of patients with MPMs. Downregulation of P14/ARF expression seems to contribute to MDM2-overexpression-mediated P53 inactivation in MPM patients.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||
Creators: |
|
||||||||||||||||||||||||||||||||||||||||
URN: | urn:nbn:de:hbz:38-410070 | ||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/bjc.2015.27 | ||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Br. J. Cancer | ||||||||||||||||||||||||||||||||||||||||
Volume: | 112 | ||||||||||||||||||||||||||||||||||||||||
Number: | 5 | ||||||||||||||||||||||||||||||||||||||||
Page Range: | S. 883 - 891 | ||||||||||||||||||||||||||||||||||||||||
Date: | 2015 | ||||||||||||||||||||||||||||||||||||||||
Publisher: | NATURE PUBLISHING GROUP | ||||||||||||||||||||||||||||||||||||||||
Place of Publication: | LONDON | ||||||||||||||||||||||||||||||||||||||||
ISSN: | 1532-1827 | ||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||
Uncontrolled Keywords: |
|
||||||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/41007 |
Downloads
Downloads per month over past year
Altmetric
Export
Actions (login required)
View Item |