gms | German Medical Science

Objective: Glioblastoma multiforme (GBM) is the most common malignant primary tumor of the central nervous system. Up to this day, patients diagnosed with GBM face an unfavorable prognosis, even with the intense standard treatment consisting of surgical resection, radiation and chemotherapy. Therefore, potential future therapeutic targets such as BRMS1, a metastasis suppressor that has been described to interact with multiple pathways regulating invasion, migration, cell survival and cell adhesion, are of high interest.

Methods: We collected a cohort of normal brain specimens (n=11, NB), adult pilocytic astrocytomas (n=4, PA), isocitratedehydrogenase– mutated gliomas WHO grade 2/3 (n= 24, IDHmut LGG) and 78 GBM. Then, we determined BRMS1 protein expression by immunohistochemical stainings and BRMS1 mRNA expression by means of qPCR, before statistically examining associations between expression patterns and retrospectively compiled tumor and patient characteristics.

Results: On protein level, we observed strong BRMS1 staining in normal cerebrum and cerebellum, whereas GBM expressed little to none. BRMS1 mRNA was overexpressed in IDHmut LGG compared to NB (p<0.01, mean 8.9 fold), PA (p<0.01, mean 8.3 fold) and GBM (p<0.01, mean 6.0 fold). When we performed GBM subgroup analysis depending on tumors’ growth pattern, local relapses (p=0.04, mean 3.5 fold), local tumors later leading to multifocal relapses (p<0.01, mean 3.9 fold) and their multifocal relapses (p<0.01, mean 3.1 fold) all displayed an overexpression of BMRS1 mRNA compared to NB. However, BRMS1 mRNA expression was neither associated with patients’ survival, nor the other obtained tumor and patient characteristics, except from a statistical correlation with the percentage of Ki67 positive cells (R=0.36, p=0.02). These observations were verified by bioinformatical analyses on a TCGA dataset

Conclusion: To conclude, BRMS1 appears to be dysregulated in gliomas. In concordance with its known mode of action, BMRS1 mRNA expression was only mild to none in GBM. We did not identify any subgroups within the tumor types based on their BRMS1 expression, however IDHmut LGG displayed a surprisingly high expression compared to the other entities. Also, there is a contrast between the BRMS1 protein and mRNA expression that hints towards post-transcritional processes regulating the BRMS1 expression, as has been described in other tumor entities. The underlying mechanisms have not been finally solved and remain a promising focus of future investigation.