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Updated: May 29, 2025
Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in
Alireza Sadeghipour1,2, Fahimeh Fattahi2,3,4, Zahra Madjd2,3
1Department of Pathology, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
Introduction:
DNA damage-inducible transcript 4 (DDIT4), induced under cellular stress conditions, has been implicated in malignancies due to its abnormal expression patterns.
Materials And Methods:
The expression of DDIT4 at the mRNA level and its potential role as a prognostic biomarker in gliomas were analyzed using the GEPIA tool. To validate these findings, DDIT4 protein expression levels and their prognostic significance were examined in tissue microarrays from glioma patients using immunohistochemistry in clinical samples.
Results:
Bioinformatics analysis revealed that DDIT4 overexpression in glioma tumors and its high mRNA expression levels are associated with poor outcomes, likely through mTOR signaling. At the protein level, positive nuclear DDIT4 expression was linked to higher histological grades and temozolomide treatment. Kaplan-Meier survival analysis demonstrated that positive nuclear DDIT4 expression is a significant predictor of poor disease-specific survival (DSS) and recurrence-free survival (RFS). Additionally, nuclear DDIT4 expression was identified as an independent prognostic factor for DSS.
Conclusion:
Our findings suggest that nuclear DDIT4 expression may serve as a potential prognostic biomarker and therapeutic target in glioma patients. However, further studies with larger sample sizes and long-term follow-ups are needed to validate these observations and confirm their clinical relevance.
Insights
DNA damage-inducible transcript 4 (DDIT4) overexpression in gliomas predicts poor patient outcomes. Nuclear DDIT4 expression is a significant prognostic biomarker for disease-specific survival and recurrence-free survival in glioma patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DNA damage-inducible transcript 4 (DDIT4) is upregulated under cellular stress and linked to various cancers.
- Abnormal DDIT4 expression patterns are observed in malignancies, suggesting a role in cancer development.
Purpose of the Study:
- To investigate the expression of DDIT4 in gliomas.
- To evaluate DDIT4 as a prognostic biomarker for glioma patients.
Main Methods:
- Bioinformatic analysis of DDIT4 mRNA expression using GEPIA.
- Immunohistochemical analysis of DDIT4 protein expression in glioma tissue microarrays.
- Kaplan-Meier survival analysis to assess prognostic significance.
Main Results:
- DDIT4 overexpression and high mRNA levels in gliomas correlate with poor patient outcomes, potentially via mTOR signaling.
- Positive nuclear DDIT4 protein expression is associated with higher tumor grades and temozolomide treatment.
- Nuclear DDIT4 expression is an independent predictor of poor disease-specific survival and recurrence-free survival.
Conclusions:
- Nuclear DDIT4 expression shows potential as a prognostic biomarker in glioma.
- DDIT4 may represent a therapeutic target for glioma patients.
- Further validation with larger cohorts and longer follow-up is warranted.
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