Biom-73. High Intra-Tumoral and Serum Matrix Metalloproteinase 9 Levels Are Associated With Reduced Survival of Glioblastoma and Brain Metastases Patients’

BACKGROUND Matrix metalloproteinase 9 (MMP-9) has been shown to promote glioblastoma invasion and the spread of brain metastases (BM). However, the current literature on its link to patient survival is inconsistent. This study investigates intra-tumoral and serum levels of MMP-9 and their correlation with overall survival (OS) in patients with glioblastoma and BM METHODS A total of 69 tumor and pre-operative serum samples were obtained from the brain tumor bank in the neurosurgery department at Soroka University Medical Center. These samples were collected from patients who underwent tumor resection from 2015 to 2021. Clinical and imaging data from 27 glioblastoma patients and 30 individuals with brain metastases were analysed, measuring and comparing their intra-tumoral and serum MMP-9 levels and activity against those of 12 meningioma patients and 23 healthy subjects. A variety of methods were used including ELISA, Gelatine Zymography, western blot and immunofluorescence. Survival analyses were conducted to investigate the correlation between MMP-9 levels, activity, and clinical parameters. RESULTS Patients with glioblastoma and BM exhibited elevated median intra-tumoral MMP-9 levels (8 ng/ml and 4 ng/ml, respectively, p<0.001), increased intra-tumoral MMP-9 activity levels, and pre-operative serum MMP-9 levels (2.8 ng/ml and 1.8 ng/ml, respectively, p<0.001). MMP-9 was present both within and among glioblastoma cells. Higher intra-tumoral and serum MMP-9 levels, but not its activity, were linked to poorer OS in glioblastoma and BM patients (15.8 versus 8.4 months, p=0.022). Notably, MMP-9 was easily detectable in the serum of the patients. CONCLUSIONS This study show that high intra-tumoral and/or serum MMP-9 levels at diagnosis are linked to significantly poorer patient OS and that intra-tumoral and serum MMP-9 may help identify glioblastoma and BM recurrence or progression. Importantly, serum MMP-9 can be monitored longitudinally and non-invasively in these patients, and a rise in levels may signal tumor progression.