ArticleJournal of neuro-oncology2023
Caspase-3 in glioma indicates an unfavorable prognosis by involving surrounding angiogenesis and tumor cell repopulation.
Article in Journal of neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 14 citations in OpenAlex.
- Illuminating the pleiotropic effects of bixin-loaded nanoemulsion on glioblastoma cell behavior through an integrated approach.Molecular biology reports · 2026Article
- The paradigm-shifting roles of caspase-3 in cancer: from death towards resuscitation.Cancer cell international · 2026Review
- The Aptamer bi-(AID-1-T) Synergizes with Radiation to Inhibit Proliferation of Human Glioma Cells.Pharmaceutics · 2025Article
- Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Radix Paeoniae Rubra Against Glioma.Applied biochemistry and biotechnology · 2024Article
- Histopathologic Changes after Yttrium-90 Radioembolization of Colorectal Liver Metastases: A Pilot Feasibility Study.Journal of vascular and interventional radiology : JVIR · 2024Article
- Role of ADP ribosylation factor guanylate kinase 1 in the malignant biological behavior of gastric cancer.Heliyon · 2024Article
- The Bi-(AID-1-T) G-Quadruplex Has a Janus Effect on Primary and Recurrent Gliomas: Anti-Proliferation and Pro-Migration.Pharmaceuticals (Basel, Switzerland) · 2024Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
aimEffective biomarkers for estimating glioma prognosis are deficient. Canonically, caspase-3 acts as an "apoptosis executioner". However, its prognostic role in glioma and mechanistic effects on prognosis remain unclear.
methodsWith glioma tissue microarrays, the prognostic roles of cleaved caspase-3 and its association with angiogenesis were explored. Next, by analyzing the mRNA microarray data from the CGGA, the prognostic role of CASP3 expression and correlations between CASP3 and markers of glioma angiogenesis and proliferation were investigated. To biologically interpret the prognostic role of caspase-3 in glioma, the influence of caspase-3 on surrounding angiogenesis and glioma cell repopulation was investigated with an in vitro cell co-culture model, which comprises irradiated U87 cells and un-irradiated firefly luciferase (Fluc)-labeled HUVEC (HUVEC-Fluc) or U87 (U87-Fluc) cells. The over-expressed dominant-negative caspase-3 was used to suppress normal caspase-3 activity.
resultsHigh levels of cleaved caspase-3 expression were associated with poor survival outcomes in glioma patients. Higher microvessel density was observed in patients with high levels of cleaved caspase-3 expression. By mining the microarray data in CGGA, it was revealed that higher CASP3 expression was found in glioma patients with lower Karnofsky Performance score, higher WHO grade, malignant histological subtype, wild-type IDH. Higher CASP3 expression indicated a worse survival rate in glioma patients. Patients with high CASP3 expression and negative IDH mutation showed the worst survival rate. Positive correlations were found between CASP3 and markers of tumor angiogenesis and proliferation. Subsequent data based on an in vitro cell co-culture model revealed that caspase-3 in irradiated glioma cells mediated pro-angiogenic and repopulation-promoting effects via regulating COX-2 signaling. With glioma tissue microarrays, high levels of COX-2 expression showed inferior survival outcomes in glioma patients. Glioma patients with high levels of cleaved caspase-3 and COX-2 expression showed the worst survival outcomes.
conclusionThis study innovatively identified an unfavorable prognostic role of caspase-3 in glioma. The pro-angiogenic and repopulation-prompting effects of caspase-3/COX-2 signaling may explain its unfavorable prognostic role and offer novel insights into therapy sensitization and curative effect prediction of glioma.
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