Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas: a study based on data mining and experimental tools

Abstract 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...

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Main Authors: Alireza Sadeghipour, Fahimeh Fattahi, Zahra Madjd, Fatemeh Tajik, Farnoosh Sedaghati, Leili Saeednejad Zanjani
Format: Article
Language:English
Published: Springer 2025-02-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-01865-0
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author Alireza Sadeghipour
Fahimeh Fattahi
Zahra Madjd
Fatemeh Tajik
Farnoosh Sedaghati
Leili Saeednejad Zanjani
author_facet Alireza Sadeghipour
Fahimeh Fattahi
Zahra Madjd
Fatemeh Tajik
Farnoosh Sedaghati
Leili Saeednejad Zanjani
author_sort Alireza Sadeghipour
collection DOAJ
description Abstract 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.
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spelling doaj-art-afb38aaba4e7484b8ea72124d36fc5c82025-02-09T12:43:29ZengSpringerDiscover Oncology2730-60112025-02-0116111910.1007/s12672-025-01865-0Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas: a study based on data mining and experimental toolsAlireza Sadeghipour0Fahimeh Fattahi1Zahra Madjd2Fatemeh Tajik3Farnoosh Sedaghati4Leili Saeednejad Zanjani5Department of Pathology, Rassoul Akram Hospital, Iran University of Medical SciencesOncopathology Research Center, Iran University of Medical Sciences (IUMS)Oncopathology Research Center, Iran University of Medical Sciences (IUMS)Oncopathology Research Center, Iran University of Medical Sciences (IUMS)Department of Pathology, School of Medicine, Iran University of Medical SciencesOncopathology Research Center, Iran University of Medical Sciences (IUMS)Abstract 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.https://doi.org/10.1007/s12672-025-01865-0DNA damage inducible transcript 4 (DDIT4)BioinformaticsGliomasImmunohistochemistry (IHC)Tissue microarray (TMA)
spellingShingle Alireza Sadeghipour
Fahimeh Fattahi
Zahra Madjd
Fatemeh Tajik
Farnoosh Sedaghati
Leili Saeednejad Zanjani
Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas: a study based on data mining and experimental tools
Discover Oncology
DNA damage inducible transcript 4 (DDIT4)
Bioinformatics
Gliomas
Immunohistochemistry (IHC)
Tissue microarray (TMA)
title Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas: a study based on data mining and experimental tools
title_full Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas: a study based on data mining and experimental tools
title_fullStr Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas: a study based on data mining and experimental tools
title_full_unstemmed Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas: a study based on data mining and experimental tools
title_short Increased nuclear expression of DNA damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas: a study based on data mining and experimental tools
title_sort increased nuclear expression of dna damage inducible transcript 4 can serve as a potential prognostic biomarker in patients with gliomas a study based on data mining and experimental tools
topic DNA damage inducible transcript 4 (DDIT4)
Bioinformatics
Gliomas
Immunohistochemistry (IHC)
Tissue microarray (TMA)
url https://doi.org/10.1007/s12672-025-01865-0
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