Integration and Comparison of Transcriptomic and Proteomic Data for Meningioma

Cancers

DavidA. Hilton¹  Rolf Warta²  Christel Herold-Mende²  C.Oliver Hanemann³  Jemma Dunn³  MatthiasE. Futschik⁴  VasileiosP. Lenis⁵ 

[1] Cellular and Anatomical Pathology, Plymouth Hospitals NHS Trust, Derriford Road, Plymouth PL6 8BU, UK;Department of Neurosurgery, Division of Experimental Neurosurgery, Heidelberg University Hospital, 69120 Heidelberg, Germany;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;Faculty of Medicine, School of Public Health, Imperial College London, Medical School, St Mary’s Hospital, Praed Street, London W2 1NY, UK;School of Health & Life Sciences, Centuria Building, Teesside University, Middlesbrough, Tees Valley TS1 3BX, UK;

关键词: meningioma;    transcriptomics;    proteomics;    data integration;    biomarker;    drug targets;   

DOI  :  10.3390/cancers12113270

来源: DOAJ

【 摘 要 】

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 FABP7, a fatty acid binding protein and the monoamine oxidase MAOB, 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 CST3, LAMP2, PACS1 and HTRA1, 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.

【 授权许可】

Unknown