Dunn Jemma, Lenis Vasileios P, Hilton David A, Warta Rolf, Herold-Mende Christel, Hanemann C Oliver, Futschik Matthias E
Faculty of Health: Medicine, Dentistry and Human Sciences, The Institute of Translational and Stratified Medicine, University of Plymouth, The John Bull Building, Plymouth Science Park, Research Way, Plymouth PL6 8BU, UK.
School of Health & Life Sciences, Centuria Building, Teesside University, Middlesbrough, Tees Valley TS1 3BX, UK.
Cancers (Basel). 2020 Nov 5;12(11):3270. doi: 10.3390/cancers12113270.
Meningioma are the most frequent primary intracranial tumour. Management of aggressive meningioma is complex, and development of effective biomarkers or pharmacological interventions is hampered by an incomplete knowledge of molecular landscape. Here, we present an integrated analysis of two complementary omics studies to investigate alterations in the "transcriptome-proteome" profile of high-grade (III) compared to low-grade (I) meningiomas. We identified 3598 common transcripts/proteins and revealed concordant up- and downregulation in grade III vs. grade I meningiomas. Concordantly upregulated genes included , a fatty acid binding protein and the monoamine oxidase , the latter of which we validated at the protein level and established an association with Food and Drug Administration (FDA)-approved drugs. Notably, we derived a plasma signature of 21 discordantly expressed genes showing positive changes in protein but negative in transcript levels of high-grade meningiomas, including the validated genes , , and , suggesting the acquisition of these proteins by tumour from plasma. Aggressive meningiomas were enriched in processes such as oxidative phosphorylation and RNA metabolism, whilst concordantly downregulated genes were related to reduced cellular adhesion. Overall, our study provides the first transcriptome-proteome characterisation of meningioma, identifying several novel and previously described transcripts/proteins with potential grade III biomarker and therapeutic significance.
脑膜瘤是最常见的原发性颅内肿瘤。侵袭性脑膜瘤的治疗很复杂，由于对分子格局的了解不完整，有效的生物标志物或药物干预措施的开发受到阻碍。在这里，我们对两项互补的组学研究进行了综合分析，以研究高级别（III级）与低级别（I级）脑膜瘤相比“转录组-蛋白质组”谱的变化。我们鉴定出3598个常见的转录本/蛋白质，并揭示了III级与I级脑膜瘤中一致的上调和下调情况。一致上调的基因包括一种脂肪酸结合蛋白和单胺氧化酶，我们在蛋白质水平上对后者进行了验证，并确定了其与美国食品药品监督管理局（FDA）批准药物的关联。值得注意的是，我们得出了一个由21个差异表达基因组成的血浆特征，这些基因在高级别脑膜瘤的蛋白质水平上呈阳性变化，但在转录水平上呈阴性变化，包括经过验证的基因、、和，这表明肿瘤从血浆中获取了这些蛋白质。侵袭性脑膜瘤在氧化磷酸化和RNA代谢等过程中富集，而一致下调的基因与细胞黏附减少有关。总体而言，我们的研究首次对脑膜瘤进行了转录组-蛋白质组特征分析，鉴定出了几种具有潜在III级生物标志物和治疗意义的新的和先前描述过的转录本/蛋白质。
