Feldheim Jonas, Kessler Almuth F, Feldheim Julia J, Schmitt Dominik, Oster Christoph, Lazaridis Lazaros, Glas Martin, Ernestus Ralf-Ingo, Monoranu Camelia M, Löhr Mario, Hagemann Carsten
Section Experimental Neurosurgery, Department of Neurosurgery, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany.
Division of Clinical Neurooncology, Department of Neurology, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, 45131 Essen, Germany.
Cancers (Basel). 2023 May 25;15(11):2907. doi: 10.3390/cancers15112907.
The metastatic suppressor BRMS1 interacts with critical steps of the metastatic cascade in many cancer entities. As gliomas rarely metastasize, BRMS1 has mainly been neglected in glioma research. However, its interaction partners, such as NFκB, VEGF, or MMPs, are old acquaintances in neurooncology. The steps regulated by BRMS1, such as invasion, migration, and apoptosis, are commonly dysregulated in gliomas. Therefore, BRMS1 shows potential as a regulator of glioma behavior. By bioinformatic analysis, in addition to our cohort of 118 specimens, we determined BRMS1 mRNA and protein expression as well as its correlation with the clinical course in astrocytomas IDH mutant, CNS WHO grade 2/3, and glioblastoma IDH wild-type, CNS WHO grade 4. Interestingly, we found BRMS1 protein expression to be significantly decreased in the aforementioned gliomas, while BRMS1 mRNA appeared to be overexpressed throughout. This dysregulation was independent of patients' characteristics or survival. The protein and mRNA expression differences cannot be finally explained at this stage. However, they suggest a post-transcriptional dysregulation that has been previously described in other cancer entities. Our analyses present the first data on BRMS1 expression in gliomas that can provide a starting point for further investigations.
转移抑制因子BRMS1与许多癌症实体中转移级联反应的关键步骤相互作用。由于胶质瘤很少发生转移,BRMS1在胶质瘤研究中一直主要被忽视。然而,其相互作用伙伴,如NFκB、VEGF或MMPs,在神经肿瘤学中却是老相识。BRMS1所调控的步骤,如侵袭、迁移和凋亡,在胶质瘤中通常失调。因此,BRMS1显示出作为胶质瘤行为调节因子的潜力。通过生物信息学分析,除了我们的118个标本队列外,我们还确定了BRMS1 mRNA和蛋白表达及其与IDH突变型星形细胞瘤、CNS WHO 2/3级以及IDH野生型胶质母细胞瘤、CNS WHO 4级临床病程的相关性。有趣的是,我们发现上述胶质瘤中BRMS1蛋白表达显著降低,而BRMS1 mRNA似乎在整体上过度表达。这种失调与患者的特征或生存无关。现阶段尚无法最终解释蛋白和mRNA表达差异。然而,它们提示了一种转录后失调,这在其他癌症实体中已有描述。我们的分析提供了关于胶质瘤中BRMS1表达的首批数据,可为进一步研究提供起点。