Protein expression of BIRC5, TK1, and TOP2A in malignant peripheral nerve sheath tumours – A prognostic test after surgical resection
Autor: | Kirsten Sundby Hall, Ben Davidson, Matthias Kolberg, Maren Høland, Nils Mandahl, Fredrik Mertens, Sigbjørn Smeland, Rolf Inge Skotheim, Guro Elisabeth Lind, Trude H. Ågesen, Ragnhild A. Lothe |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Oncology
Male Cancer Research Pathology Survivin Inhibitor of Apoptosis Proteins TK1 Poly-ADP-Ribose Binding Proteins Peripheral Nerve Sheath Research Articles Aged 80 and over biology BIRC5 Soft tissue General Medicine Middle Aged Prognosis Immunohistochemistry Neoplasm Proteins DNA-Binding Proteins Gene Expression Regulation Neoplastic Survival Rate Molecular Medicine Female Neurilemmoma Research Article Adult medicine.medical_specialty Adolescent Thymidine Kinase Disease-Free Survival MPNST Antigens Neoplasm Internal medicine Genetics medicine Humans Neurofibromatosis Thymidine kinase 1 Aged Retrospective Studies Topoisomerase TOP2A medicine.disease Clinical trial DNA Topoisomerases Type II biology.protein Genome-Wide Association Study |
Zdroj: | Molecular Oncology |
ISSN: | 1878-0261 1574-7891 |
Popis: | No consensus treatment regime exists beyond surgery for malignant peripheral nerve sheath tumours (MPNST), and the purpose of the present study was to find new approaches to stratify patients with good and poor prognosis and to better guide therapeutic intervention for this aggressive soft tissue cancer. From a total of 67 MPNSTs from Scandinavian patients with and without neurofibromatosis type 1, 30 MPNSTs were investigated by genome-wide RNA expression profiling and 63 MPNSTs by immunohistochemical (IHC) analysis, and selected genes were submitted to analyses of disease-specific survival. The potential drug target genes survivin (BIRC5), thymidine kinase 1 (TK1), and topoisomerase 2-alpha (TOP2A), all encoded on chromosome arm 17q, were up-regulated in MPNST as compared to benign neurofibromas. Each of them was found to be independent prognostic markers on the gene expression level, as well as on the protein level. A prognostic profile was identified by combining the nuclear expression scores of the three proteins. For patients with completely resected tumours only 15% in the high risk group were alive after two years, as compared to 78% in the low risk group. In conclusion, we found a novel protein expression profile which identifies MPNST patients with inferior prognosis even after assumed curative surgery. The tested proteins are drug targets; therefore the expression profile may provide predictive information guiding the design of future clinical trials. Importantly, as the effect is seen on the protein level using IHC, the biomarker panel can be readily implemented in routine clinical testing. |
Databáze: | OpenAIRE |
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