High cytoplasmic FOXO1 and pFOXO1 expression in astrocytomas are associated with worse surgical outcome
Related Experiment Video
Updated: May 9, 2026
Generation and Characterization of Human Induced Pluripotent Stem Cell-derived Astrocytes Lacking Fragile X Messenger Ribonucleoprotein
Published on: June 6, 2025
Chao Chen1, Tao Xu, Jinxu Zhou
1Department of Neurosurgery, Shanghai Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Abstract:
FOXO1 is at a convergence point of receptor tyrosine kinase (RTK) signaling, which is one of the three core pathways implicated in glioblastoma. It was recently shown that FOXO1 can effectively induce glioma cell death and inhibit tumor growth through cell cycle arrest and apoptosis. We therefore evaluated FOXO1 and pFOXO1 protein expression in 181 primary astrocytoma samples and 16 normal brain samples. Astrocytoma samples expressed higher cytoplasmic FOXO1 and pFOXO1 than normal brain samples. Nuclear pFOXO1 level was significantly higher than nuclear FOXO1 in astrocytomas. High cytoplasmic FOXO1 expression was associated with older onset age (P = 0.001) and higher WHO grade (P = 0.001). The trend was also observed between cytoplasmic pFOXO1 expression and WHO grade although not significant. Univariate survival analysis showed that both high cytoplasmic FOXO1 and pFOXO1 expression indicated a significantly shorter median overall survival and progression-free survival. Multivariate survival analysis revealed cytoplasmic FOXO1 expression, cytoplasmic pFOXO1 expression, WHO grade, gender, extent of resection and radiotherapy to be independent prognostic factors for overall survival and progression-free survival. Thus, our data suggested that cytoplasmic FOXO1 and pFOXO1 expression may serve as valuable prognostic variables in astrocytomas and may have significant implications for the development and application of targeted therapy.
Insights
Cytoplasmic FOXO1 and phosphorylated FOXO1 (pFOXO1) protein levels are elevated in astrocytomas, correlating with tumor grade and poorer survival outcomes. These findings suggest FOXO1 pathway alterations are key prognostic indicators for glioblastoma patients.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Signaling Pathways
Background:
- Glioblastoma involves receptor tyrosine kinase (RTK) signaling, with FOXO1 identified as a key regulator.
- FOXO1 demonstrates potential in inducing glioma cell death via cell cycle arrest and apoptosis.
Purpose of the Study:
- To investigate FOXO1 and pFOXO1 protein expression in astrocytomas.
- To correlate expression levels with clinicopathological features and patient survival.
Main Methods:
- Analysis of FOXO1 and pFOXO1 protein expression in 181 primary astrocytoma and 16 normal brain samples.
- Statistical analysis including univariate and multivariate survival analyses.
Main Results:
- Astrocytomas showed increased cytoplasmic FOXO1 and pFOXO1 compared to normal brain tissue.
- Higher cytoplasmic FOXO1 correlated with older age and higher WHO grade.
- Elevated cytoplasmic FOXO1 and pFOXO1 predicted significantly shorter overall and progression-free survival.
- Cytoplasmic FOXO1, pFOXO1, WHO grade, gender, resection extent, and radiotherapy were independent prognostic factors.
Conclusions:
- Cytoplasmic FOXO1 and pFOXO1 expression are valuable prognostic markers in astrocytomas.
- These findings have implications for targeted therapies in glioblastoma treatment.
