Algorithmically Deduced Molecular Pathway Is a Potent Grade and Survival Biomarker of Human Gliomas.

Gliomas are the most common malignant brain tumors with high mortality rates. Recently we showed that the gene has a role in glioblastoma progression. Here we reconstructed the molecular pathway using the human interactome model. We assessed the biomarker capacity of 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 pathway showed strong biomarker characteristics and significantly outperformed the expression level itself. For all relevant datasets, it could robustly discriminate GBM and LGG ( < 1.63 × 10, AUC > 0.74). High pathway activation level was associated with poor OS in LGG ( < 0.001), and low PFS in LGG ( < 0.001) and GBM ( < 0.05). pathway activation level was poor prognosis biomarker for OS ( < 0.05) and PFS ( < 0.05) in LGG with mutation, for PFS in LGG with wild type ( < 0.001) and mutant with 1p/19q codeletion( < 0.05), in GBM with unmethylated ( < 0.05), and in GBM with wild type ( < 0.05). Thus, we conclude that the activation level of the pathway is a potent new-generation diagnostic and prognostic biomarker for multiple molecular subtypes of GBM and LGG.