Risk of glioma malignant progression after biopsy-induced oncotaxis — a systematic review

Introduction. Glioma biopsy remains the cornerstone of diagnosis and treatment planning. However, increasing evidence suggests that biopsy-induced tissue disruption and inflammatory responses may accelerate tumor progression and malignant transformation. Objectives. To systematically review clinical and preclinical evidence regarding the biological mechanisms and risks of glioma malignant transformation after biopsy. Material and methods. A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane Library (2000–2024). Eligible studies included clinical reports, experimental models, and mechanistic studies investigating glioma progression, invasion, or malignant transformation following biopsy or surgical trauma. Data extraction was performed independently by two reviewers. Risk of bias was assessed using ROBINS-I for non-randomized clinical studies and SYRCLE’s tool for animal studies. Results. Of 732 records identified, 24 studies met eligibility criteria. Mechanistic studies demonstrated that biopsy-induced trauma initiates epithelial-mesenchymal transition (EMT), upregulates matrix metalloproteinases (MMP-2, MMP-9), and activates hypoxia-inducible pathways, thereby enhancing glioma cell motility and invasion. The CXCL12/CXCR4 axis and TRP channels (TRPV1, TRPV4, TRPM7) were consistently implicated in post-biopsy oncotaxis. Clinical evidence indicated that neutrophil infiltration and inflammatory cytokines promote glioblastoma progression after biopsy, and case reports described rapid transformation of low-grade gliomas to glioblastoma. Nonetheless, study heterogeneity and lack of prospective controlled designs limited the strength of causal inference. Conclusions. Biopsy-induced inflammatory and molecular responses may contribute to glioma aggressiveness and malignant progression. Minimizing tissue disruption during biopsy and developing adjunctive anti-inflammatory strategies should be prioritized in future research.