Abstract
Angiogenesis is one of the key features of glioblastoma (GB). However, the use of anti-angiogenic therapies directed against vascular endothelial growth factor (VEGF) is limited by primary or acquired resistance. MET/HGF and PlGF signaling are involved in potential alternative escape mechanisms to VEGF pathway. Our objective was to explore the potential changes of MET/HGF and PlGF expression, comparing initial diagnosis and recurrence after radiotherapy-temozolomide (RT/TMZ). Paired frozen tumors from both initial and recurrent surgery after radio-chemotherapy were available for 28 patients. RNA expressions of PlGF, MET, and HGF genes were analyzed by RT-qPCR. PlGF expression significantly decreased at recurrence (p = 0.021), and expression of MET showed a significant increase (p = 0.011) at recurrence. RNA expressions of MET and HGF significantly correlated both at baseline and recurrence (baseline: p = 0.005; recurrence: p = 0.019). Evolutive profile (increasing versus decreasing expression at recurrence) of MET was associated with PFS (p = 0.002) and OS (p = 0.022) at recurrence, while the evolutive profile of HGF was associated with PFS at relapse (p = 0.049). Recurrence of GB after chemo-radiation could be associated with a variation in PlGF and MET expression. These results contribute to suggest a modification of the GB angiogenic process between initial diagnosis and recurrence.
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SIRIC Grant: INCa-DGOS-Inserm 6038, ARTC-Sud, APHM Tumor Bank (authorization number AC-2013–1786).
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Tabouret, E., Denicolai, E., Delfino, C. et al. Changes in PlGF and MET-HGF expressions in paired initial and recurrent glioblastoma. J Neurooncol 130, 431–437 (2016). https://doi.org/10.1007/s11060-016-2251-5
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DOI: https://doi.org/10.1007/s11060-016-2251-5