ArticleActa neuropathologica communications2022
Plasmatic MMP9 released from tumor-infiltrating neutrophils is predictive for bevacizumab efficacy in glioblastoma patients: an AVAglio ancillary study.
Article in Acta neuropathologica communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00943826 (A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Trial of Bevacizumab, Temozolomide and Radiotherapy, Followed by Bevacizumab and Temozolomide Versus Placebo, Temozolomide and Radiotherapy Followed by Placebo and Temozolomide in Patients With Newly Diagnosed Glioblastoma), which is not on this map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Trial of Bevacizumab, Temozolomide and Radiotherapy, Followed by Bevacizumab and Temozolomide Versus Placebo, Temozolomide and Radiotherapy Followed by Placebo and Temozolomide in Patients With Newly Diagnosed Glioblastoma
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Glioblastoma invasion patterns from a clinical perspective-a systematic review.Neurosurgical review · 2024Pooled it
- Integrated Analysis of Glycolytic and Cholesterogenic Genes Identifies Prognostic Metabolic Subgroup of IDH Wild-Type Glioblastoma.Cancer medicine · 2026Article
- Vascular SMC-like CAF-derived THBS1 drives tumor-associated neutrophil recruitment to orchestrate an immunosuppressive microenvironment in gastric cancer.Cell death & disease · 2026Article
- Review
- Role of matrix metalloproteinases in the invasion of glioblastoma and drug interventions (Review).International journal of molecular medicine · 2026Review
- Understanding Neovascularization in Glioblastoma: Insights from the Current Literature.International journal of molecular sciences · 2025Review
- High intra-tumoral and serum matrix metalloproteinase 9 levels are associated with reduced survival of patients with glioblastoma and brain metastases.Frontiers in oncology · 2025Article
- Treatment mechanism and research progress of bevacizumab for glioblastoma.American journal of cancer research · 2025Review
- The diverse roles of neutrophils from protection to pathogenesis.Nature immunology · 2024Review
- Matrix metalloproteinase 9 expression and glioblastoma survival prediction using machine learning on digital pathological images.Scientific reports · 2024Article
- Glioblastoma microenvironment-from biology to therapy.Genes & development · 2024Review
- Association between the Anatomical Location of Glioblastoma and Its Evaluation with Clinical Considerations: A Systematic Review and Meta-Analysis.Journal of clinical medicine · 2024Review
- Phase 1 dose expansion and biomarker study assessing first-in-class tumor microenvironment modulator VT1021 in patients with advanced solid tumors.Communications medicine · 2024Article
- Aspartame carcinogenic potential revealed through network toxicology and molecular docking insights.Scientific reports · 2024Article
- Proteometabolomics of initial and recurrent glioblastoma highlights an increased immune cell signature with altered lipid metabolism.Neuro-oncology · 2024Article
- Association Between Diverse Cell Death Patterns Related Gene Signature and Prognosis, Drug Sensitivity, and Immune Microenvironment in Glioblastoma.Journal of molecular neuroscience : MN · 2024Article
- Post-Translational Modifications in Tau and Their Roles in Alzheimer's Pathology.Current Alzheimer research · 2024Review
- Common diagnostic biomarkers and molecular mechanisms ofFrontiers in immunology · 2024Article
- Recent Developments in Blood Biomarkers in Neuro-oncology.Current neurology and neuroscience reports · 2023Review
- Deciphering the Action of Neuraminidase in Glioblastoma Models.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously identified matrix metalloproteinase 2 (MMP2) and MMP9 plasma levels as candidate biomarkers of bevacizumab activity in patients with recurrent glioblastoma. The aim of this study was to assess the predictive value of MMP2 and MMP9 in a randomized phase III trial in patients with newly diagnosed glioblastoma and to explore their tumor source. In this post hoc analysis of the AVAglio trial (AVAGlio/NCT00943826), plasma samples from 577 patients (bevacizumab, n = 283; placebo, n = 294) were analyzed for plasma MMP9 and MMP2 levels by enzyme-linked immunosorbent assay. A prospective local cohort of 38 patients with newly diagnosed glioblastoma was developed for analysis of tumor characteristics by magnetic resonance imaging and measurement of plasma and tumor levels of MMP9 and MMP2. In this AVAglio study, MMP9, but not MMP2, was correlated with bevacizumab efficacy. Patients with low MMP9 derived a significant 5.2-month overall survival (OS) benefit with bevacizumab (HR 0.51, 95% CI 0.34-0.76, p = 0.0009; median 13.6 vs. 18.8 months). In multivariate analysis, a significant interaction was seen between treatment and MMP9 (p = 0.03) for OS. In the local cohort, we showed that preoperative MMP9 plasma levels decreased after tumor resection and were correlated with tumor levels of MMP9 mRNA (p = 0.03). However, plasma MMP9 was not correlated with tumor size, invasive pattern, or angiogenesis. Using immunohistochemistry, we showed that MMP9 was expressed by inflammatory cells but not by tumor cells. After cell sorting, we showed that MMP9 was expressed by CD45+ immune cells. Finally, using flow cytometry, we showed that MMP9 was expressed by tumor-infiltrating neutrophils. In conclusion, circulating MMP9 is predictive of bevacizumab efficacy and is released by tumor-infiltrating neutrophils.
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