Emerging multi-omics biomarkers in glioblastoma: Integrative insights from genomics to metabolomics

Glioblastoma (GBM) is the most malignant form of primary brain tumor in adults, described by profound molecular heterogeneity, rapid progression, and limited therapeutic response. Despite advances in chemotherapy (TMZ), radiotherapy, and surgery, patient outcomes remain poor, with a median survival of 12-15 months. Traditional single-omics studies have identified critical biomarkers such as IDH mutations, MGMT promoter methylation, and EGFR alterations; however, these provide only partial insight into the disease's complexity. Recent integrative multi-omics approaches encompassing genomics, transcriptomics, epigenomics, proteomics, metabolomics, and non-coding RNAs have transformed the landscape of biomarker discovery in GBM. Genomic profiling has revealed recurrent mutations and subtype-specific aberrations, while transcriptomic analyses refine molecular classification and uncover alternative splicing and fusion events. Epigenomic markers, particularly MGMT methylation and G-CIMP status, are now central to prognosis and therapy stratification. Proteomic and metabolomic studies highlight dysregulated pathways, metabolic vulnerabilities, and non-invasive biomarkers in cerebrospinal fluid and plasma. Integrating multi-omics data not only improves diagnostic and prognostic accuracy but also unveils therapeutic targets, offering opportunities for precision oncology. Furthermore, liquid biopsy and single-cell/spatial omics enhance real-time monitoring of disease progression and treatment response, addressing challenges posed by intratumoral heterogeneity. This review synthesizes recent advances in GBM biomarker research across multiple omics layers, emphasizing their complementary roles in unravelling tumor biology, guiding personalized treatment, and shaping future therapeutic strategies.