AUTHOR=Bu Fan , Zhong Jifa , Guan Ruiqian TITLE=Biomarkers in glioblastoma and degenerative CNS diseases: defining new advances in clinical usefulness and therapeutic molecular target JOURNAL=Frontiers in Molecular Biosciences VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1506961 DOI=10.3389/fmolb.2025.1506961 ISSN=2296-889X ABSTRACT=BackgroundDiscovering biomarkers is central to the research and treatment of degenerative central nervous system (CNS) diseases, playing a crucial role in early diagnosis, disease monitoring, and the development of new treatments, particularly for challenging conditions like degenerative CNS diseases and glioblastoma (GBM).MethodsThis study analyzed gene expression data from a public database, employing differential expression analyses and Gene Co-expression Network Analysis (WGCNA) to identify gene modules associated with degenerative CNS diseases and GBM. Machine learning methods, including Random Forest, Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine - Recursive Feature Elimination (SVM-RFE), were used for case-control differentiation, complemented by functional enrichment analysis and external validation of key genes.ResultsNinety-five commonly altered genes related to degenerative CNS diseases and GBM were identified, with RELN and GSTO2 emerging as significant through machine learning screening. Receiver operating characteristic (ROC) analysis confirmed their diagnostic value, which was further validated externally, indicating their elevated expression in controls.ConclusionThe study’s integration of WGCNA and machine learning uncovered RELN and GSTO2 as potential biomarkers for degenerative CNS diseases and GBM, suggesting their utility in diagnostics and as therapeutic targets. This contributes new perspectives on the pathogenesis and treatment of these complex conditions.