Algorithmically Deduced <i>FREM2</i> Molecular Pathway Is a Potent Grade and Survival Biomarker of Human Gliomas

Abstract

Gliomas are the most common malignant brain tumors with high mortality rates. Recently we showed that the FREM2 gene has a role in glioblastoma progression. Here we reconstructed the FREM2 molecular pathway using the human interactome model. We assessed the biomarker capacity of FREM2 expression and its pathway as the overall survival (OS) and progression-free survival (PFS) biomarkers. To this end, we used three literature and one experimental RNA sequencing datasets collectively covering 566 glioblastomas (GBM) and 1097 low-grade gliomas (LGG). The activation level of deduced FREM2 pathway showed strong biomarker characteristics and significantly outperformed the FREM2 expression level itself. For all relevant datasets, it could robustly discriminate GBM and LGG (p −13, AUC > 0.74). High FREM2 pathway activation level was associated with poor OS in LGG (p p p FREM2 pathway activation level was poor prognosis biomarker for OS (p p IDH mutation, for PFS in LGG with wild type IDH (p IDH with 1p/19q codeletion(p MGMT (p IDH (p FREM2 pathway is a potent new-generation diagnostic and prognostic biomarker for multiple molecular subtypes of GBM and LGG.

Keywords

• <i>FREM2</i>
• glioma
• glioblastoma
• survival prognosis
• algorithmically deduced molecular pathway
• transcriptomics