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Downregulation of RKIP is associated with poor outcome and malignant progression in gliomas
Olga Martinho1, Sara Granja, Teresa Jaraquemada
1Life and Health Sciences Research Institute, Health Sciences School, University of Minho, Braga, Portugal.
Abstract:
Malignant gliomas are highly infiltrative and invasive tumors, which precludes the few treatment options available. Therefore, there is an urgent need to elucidate the molecular mechanisms underlying gliomas aggressive phenotype and poor prognosis. The Raf Kinase Inhibitory protein (RKIP), besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis and prognosis in several human neoplasms. Its role in the prognosis and tumourigenesis of gliomas remains unclear. In the present study, we found that RKIP protein is absent in a low frequency (10%, 20/193) of glioma tumors. Nevertheless, the absence of RKIP expression was an independent prognostic marker in glioma. Additionally, by in vitro downregulation of RKIP, we found that RKIP inhibition induces a higher viability and migration of the cells, having no effect on cellular proliferation and angiogenesis, as assessed by in vivo CAM assay. In conclusion, this is the largest series studied so far evaluating the expression levels of this important cancer suppressor protein in glioma tumors. Our results suggest that in a subset of tumors, the absence of RKIP associates with highly malignant behavior and poor survival of patients, which may be a useful biomarker for tailored treatment of glioma patients.
Insights
Absence of Raf Kinase Inhibitory protein (RKIP) in glioma tumors correlates with aggressive cancer behavior and poor patient survival. This finding suggests RKIP absence may serve as a biomarker for targeted glioma treatments.
Area of Science:
- Neuro-oncology
- Cancer biology
- Molecular mechanisms of cancer
Background:
- Malignant gliomas are aggressive, infiltrative tumors with limited treatment options.
- Understanding glioma's molecular drivers is crucial for improving patient prognosis.
- Raf Kinase Inhibitory protein (RKIP) impacts cancer progression and metastasis in various neoplasms, but its role in gliomas is undefined.
Purpose of the Study:
- To investigate the expression and prognostic significance of RKIP in glioma.
- To elucidate the functional role of RKIP in glioma cell behavior.
Main Methods:
- Analysis of RKIP protein expression in 193 glioma tumors.
- In vitro RKIP downregulation studies in glioma cells.
- In vivo chick chorioallantoic membrane (CAM) assay for angiogenesis.
Main Results:
- RKIP protein was absent in 10% of glioma tumors.
- Absence of RKIP expression independently predicted poor prognosis in glioma patients.
- RKIP inhibition in vitro increased glioma cell viability and migration.
- RKIP inhibition did not affect glioma cell proliferation or angiogenesis.
Conclusions:
- This study represents the largest evaluation of RKIP in glioma to date.
- RKIP absence is associated with malignant glioma behavior and reduced patient survival.
- RKIP may serve as a valuable biomarker for personalized glioma treatment strategies.
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