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

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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:
CreatorsEmailORCIDORCID Put Code
Walter, R. F. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mairinger, F. D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ting, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vollbrecht, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mairinger, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Theegarten, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christoph, D. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmid, K. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wohlschlaeger, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
ARF TUMOR-SUPPRESSOR; EMBRYONIC LETHALITY; IN-VIVO; THYMIDYLATE SYNTHASE; MDM2-DEFICIENT MICE; MUTATIONAL ANALYSIS; PROTEIN EXPRESSION; CHEMOTHERAPY; PATHWAY; GENESMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41007

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