Prospective Cohort of Patients With Newly Diagnosed Glioblastoma: Analysis of MMP2 and MMP9 Expression and Correlation to Neuro-imaging Features.

Glioblastoma is the most frequent and aggressive primary brain tumor in adults. A team recently showed that baseline plasma levels of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) were correlated to bevacizumab activity in patients with recurrent glioblastoma. To date, the biological rationale of this results remains unknown but MMP2 could be involved in classical angiogenesis while MMP9 could promote vasculogenesis.

The objectives are to correlate the plasma levels of MMP2 and MMP9 to their Ribonucleic acid (RNA) and protein tissue expression, activity and to patient neuro-imaging features. To analyze the changes of MMP2 and MMP9 plasma levels during peri-operative period and after radio-chemotherapy.

Methods: Plasmatic levels of MMP2, MMP9, vascular endothelial growth factor-A (VEGFA), vascular endothelial growth factor-R2 (VEGFR2), stromal cell-derived factor 1 (SDF1) and chemokine receptor-4 (CXCR4) will be analyzed by enzyme-linked immunosorbent assay (ELISA) in pre-, post-operative period, before radiotherapy, before adjuvant temozolomide and at relapse in newly diagnosed glioblastoma. RNA expression of these factors will be analyzed by reverse transcription-Polymerase chain reaction (RT-qPCR) on frozen tumor samples, whereas protein expression will be analyzed by ELISA and immunohistochemistry. Enzymatic activity of MMP2 and MMP9 will be analyzed by zymography. Tumor volume, infiltration and perfusion degrees will be analyzed on Magnetic Resonance Imaging (MRI) performed before and after surgery and before adjuvant temozolomide. Neuro-imaging characteristics will be correlated to plasma and tissue expressions of these factors.

The expected results are to better define the expression profile of MMP2, MMP9 and the change in their plasma level during treatment, a prerequisite for their clinical use.