Wild-Type TP53 Predicts Poor Prognosis in Lower-Grade Glioma via TP53-CXCL14-GATA3 Axis
Amr Ahmed El-Arabey1,2, Samia S Alkhalil3, Nouf Omar AlAfaleq4
1Applied College, King Khalid University, P. O. Box 9004, 61413, Abha, Saudi Arabia. ph.amrcapa@gmail.com.
Journal of Molecular Neuroscience : MN
|March 19, 2025
Summary
Wild-type Tumor Protein p53 (TP53) is common in low-grade gliomas (LGG) and linked to worse outcomes. This TP53 status influences microRNAs, immune cells, and adipose tissue, suggesting a predictive axis for LGG patient prognosis.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Genomics
Background:
- Low-grade gliomas (LGG) are common pediatric central nervous system tumors.
- Tumor Protein p53 (TP53) is crucial in DNA damage and repair pathways.
- The clinical significance of TP53 status in LGG remains unclear.
Purpose of the Study:
- To investigate the impact of TP53 status on LGG patient outcomes.
- To analyze TP53's effect on molecular signatures (chemokines, microRNAs) and immune infiltration in LGG.
- To explore the prognostic value of TP53 in the tumor microenvironment.
Main Methods:
- Analysis of clinical data from The Cancer Genomic Atlas (TCGA) LGG cohort.
- Assessment of TP53 mutation status and its correlation with clinical parameters.
- Evaluation of chemokine and microRNA expression patterns in relation to TP53 status.
- Analysis of immune cell infiltration and adipose tissue characteristics.
Main Results:
- Wild-type TP53 is the predominant phenotype in LGG and associated with poorer clinical outcomes.
- TP53 status significantly correlates with clinical parameters like age, gender, and stage.
- Wild-type TP53 influences prognostic microRNAs (e.g., has-miR-10a-3p, has-miR-155-5p) and chemokine ligand 14 (CXCL14) expression.
- TP53 status affects immune cell infiltration (M1 macrophages, CD8+ T cells) via GATA Binding Protein 3 (GATA3) and Fatty Acid Synthase (FASN) modulation.
- The TP53-CXCL14-GATA3 axis shows potential for predicting outcomes in wild-type TP53 LGG.
Conclusions:
- Wild-type TP53 status is a significant indicator of poor prognosis in LGG patients.
- TP53 influences the tumor microenvironment, including immune cell infiltration and molecular signatures.
- The identified TP53-CXCL14-GATA3 axis offers a potential biomarker for predicting LGG outcomes.
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