Article
Are there correlations between clinical patient data and molecular expression profiles of the key RTK/MAP kinase & AKT/mTOR signaling pathways in human meningiomas?
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Authors
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Jan Walter
- Department of Neurosurgery, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany
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Diana Freitag
- Department of Neurosurgery, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany
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Fanny Rapp
- Department of Neurosurgery, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany
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Susanne Grube
- Department of Neurosurgery, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany
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Rolf Kalff
- Department of Neurosurgery, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany
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Christian Ewald
- Department of Neurosurgery, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany
| Published: | June 8, 2016 |
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Outline
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Objective: PI3K/Akt/mTOR and RTK/MAPK pathways propagate tumor proliferation and are constantly over-/activated in numerous tumors. In meningiomas gene expression analysis of those pathways revealed intriguing differences in individual expression profiles independent of the WHO-grade. To assess the potential use of targeted RTK-/mTOR-inhibitors this study analyzed correlations between clinical patient data and individual molecular expression profiles of their tumors.
Method: In 75 meningiomas (WHO I°-III°) expression of PDGFRbeta, VEGFR-2, pan-Ras, B-Raf, ERK1, ERK2, Akt1 and mTOR was determined by qPCR and analysed by the dd ct method in comparison to leptomeningeal tissue and correlated with the individual tumor WHO-grade, edema, size and location as well as clinical patient data like age, sex, co-morbidities, and co-medication. Mixed linear model was used for statistical analysis.
Results: Individual differences in expression profiles of all target genes were found. Surprisingly there were no significant variations of these expressions in correlation with the WHO-grade or the tumor properties like size, location, and degree of peritumoral edema. Looking at the individual patient data, this study reveals correlations between gene expression profiles of both pathways and a female sex as well as an age dependency.
Conclusions: Analyzing a larger group of meningiomas for gene expression of the PI3K/Akt/mTor & RTK signaling cascades revealed differences to non-pathological leptomeningeal tissue, but no WHO grade dependency. Correlations between a subgroup of clinical patient data, like sex and age and the individual molecular expression pattern may lead the way to a more targeted tumor therapy stratified according to WHO-grade independent parameters.
