Gjorgjevski Marko, Hannen Ricarda, Carl Barbara, Li Yu, Landmann Emilie, Buchholz Malte, Bartsch Jörg W, Nimsky Christopher
Department of Neurosurgery, Philipps University Marburg, Baldingerstr., 35033 Marburg, Germany.
Clinic for Gastroenterology, ZTI, Philipps University Marburg, Hans-Meerwein Str. 3, 35043 Marburg, Germany.
Biosci Rep. 2019 Jun 20;39(6). doi: 10.1042/BSR20182361. Print 2019 Jun 28.
Due to poor prognosis of glioblastoma (GBM), there is an urgent need to develop new therapeutic strategies. Besides eliminating GBM tumor cells and stem cells, a novel therapeutic approach aims to target Glioma-associated microglia/macrophages (GAMs). We investigated the molecular profile of GAMs correlated with patient prognosis by exploiting M1/M2-like polarization markers in a cohort of 20 GBM patients. Using quantitative PCR (qPCR), the markers CXCL10 (M1) and CCL13 (M2) were validated in human macrophages and applied to a global analysis of GBM tissue. Furthermore, proteinase genes, known to be associated with GBM progression (), were analyzed in correlation to M1/M2 markers. Notably, expression levels of and are significantly correlated with an M1-like phenotype and are positively associated to patient survival. Whilst ADAM8 mRNA expression was equally correlated with M1- and M2-like markers, genes for and are significantly associated with an M2-like phenotype and association to impaired prognosis in the GBM patient cohort. Thus, we provide a robust and reliable combination of qPCR markers to characterize global microglia/macrophage status and the associated proteinase profiles in GBM patients that can be used to analyze the tumor microenvironment, the patients' prognosis and preselect those GBM patients for which targeting the microglia/macrophage population by repolarization might be beneficial.
由于胶质母细胞瘤(GBM)预后较差,迫切需要开发新的治疗策略。除了消除GBM肿瘤细胞和干细胞外,一种新的治疗方法旨在靶向胶质瘤相关的小胶质细胞/巨噬细胞(GAMs)。我们通过利用20例GBM患者队列中的M1/M2样极化标记物,研究了与患者预后相关的GAMs分子特征。使用定量PCR(qPCR),CXCL10(M1)和CCL13(M2)标记物在人巨噬细胞中得到验证,并应用于GBM组织的全面分析。此外,分析了已知与GBM进展相关的蛋白酶基因与M1/M2标记物的相关性。值得注意的是,[具体基因1]和[具体基因2]的表达水平与M1样表型显著相关,并且与患者生存率呈正相关。虽然ADAM8 mRNA表达与M1和M2样标记物同样相关,但[具体基因3]和[具体基因4]与M2样表型显著相关,并且与GBM患者队列中预后不良相关。因此,我们提供了一种强大且可靠的qPCR标记物组合,用于表征GBM患者的整体小胶质细胞/巨噬细胞状态和相关蛋白酶谱,可用于分析肿瘤微环境、患者预后,并预先选择那些通过重新极化靶向小胶质细胞/巨噬细胞群体可能有益的GBM患者。