Abstract
Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Despite advances in treatment, mechanisms underlying GBM invasion remain incompletely understood. This systematic review synthesizes findings from laboratory and clinical studies to elucidate the molecular mechanisms driving GBM invasion and their implications for prognosis and therapy. This review adhered to PRISMA guidelines, conducting a comprehensive search of PubMed/Medline for studies published up to October 16, 2023. Inclusion criteria focused on studies investigating molecular mechanisms of GBM invasiveness with reported clinical outcomes (overall survival (OS) and progression-free survival (PFS). Exclusion criteria included systematic reviews, case reports, small case series, and studies limited to preclinical data. Risk of bias was assessed using the ROBINS-I tool. From 831 records, 21 studies (2198 patients) met the criteria. Key GBM invasion mechanisms included ECM degradation, vascular invasion, EMT, apoptotic regulation, cytoskeletal organization, and RNA sequencing. Vascular mechanisms were most studied. Bevacizumab resistance linked to poorer outcomes. EMT markers like TWIST and ECM degradation via MMPs such as CD147 correlated with decreased survival. Cytoskeletal and RNA studies highlighted the prognostic significance of tumor subtypes and microenvironmental interactions. This systematic review elucidates the molecular mechanisms underlying GBM invasiveness and their clinical implications. Integrating molecular profiling into routine clinical assessment may enhance prognostic accuracy and therapeutic efficacy, paving the way for personalized treatment strategies.