Medical Student Cooper Medical School Montville, New Jersey, United States
Introduction: The membranome – constituent of genes coding for proteins with plasma membrane associations – has long been recognized to play an important role in the development and maintenance of human glioblastoma multiforme (GBM). Cell lines are commonly used in vitro to mimic GBM in the research setting, but the extent to which they resemble GBM tumors in relation to the membranome remains poorly understood.
Methods: Bulk mRNA-sequencing data and corresponding annotation files were retrieved from Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA). The membranome was classified as the set of genes with protein products integrated with or covalently associated with the plasma cell membrane. Genes shared between CCLE and TCGA were screened by gene ontology analysis and the Membranome 2.0 database. Additional filtering was performed for genes coding for proteins that localize to intracellular compartments, additional membranomic proteins (e.g., GPI-anchored proteins), and genes that correlated significantly with tumor purity scores. The remaining top 3000 genes based on interquartile range were used for downstream Spearman correlation analysis. Furthermore, differential expression testing was conducted following by gene set enrichment analysis was implemented to examine changes in gene and pathway expression between GBM tumors and cell lines.
Results: Some commonly used GBM cell lines, including AM38 and U87MG, share little with the membranome expression profile of clinical GBM. Enrichment analysis revealed that numerous genes related to neurexin/neuroligin, ion homeostasis, and synaptic signaling were significantly downregulated in the cell line membranome compared to the tumor membranome.
Conclusion : Our findings demonstrate that the membranome of common GBM cell lines may not be wholly representative of the GBM disease state.
