Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validation

Abstract Background Low-grade glioma (LGG) is a primary brain tumor with relatively low malignancy. NCOA4 is a key regulator of ferritinophagy-related processes and is involved in the occurrence and development of many cancers. However, the role of NCOA4 in LGG remains poorly understood. Methods Thi...

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Main Authors: Guangtang Chen, Xueping Shi, Rukai Jiao, Jiacai Qian, Xiaolin Du, Jian Liu, Xi Zeng
Format: Article
Language:English
Published: BMC 2025-01-01
Series:BMC Neurology
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Online Access:https://doi.org/10.1186/s12883-025-04036-4
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author Guangtang Chen
Xueping Shi
Rukai Jiao
Jiacai Qian
Xiaolin Du
Jian Liu
Xi Zeng
author_facet Guangtang Chen
Xueping Shi
Rukai Jiao
Jiacai Qian
Xiaolin Du
Jian Liu
Xi Zeng
author_sort Guangtang Chen
collection DOAJ
description Abstract Background Low-grade glioma (LGG) is a primary brain tumor with relatively low malignancy. NCOA4 is a key regulator of ferritinophagy-related processes and is involved in the occurrence and development of many cancers. However, the role of NCOA4 in LGG remains poorly understood. Methods This study comprehensively analyzed several mainstream bioinformatics databases to explore the expression, diagnostic efficacy, clinical pathological features, immune infiltration, prognostic value, and biological functions of NCOA4 in LGG. Immunohistochemistry experiments were conducted using LGG tissue samples collected from our hospital to validate the bioinformatics analysis results. Results NCOA4 expression was significantly elevated in LGG (p < 0.05), with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.973, suggesting it as a potential diagnostic marker. High NCOA4 expression was associated with younger age (21–40 years), lower malignancy (oligodendroglioma), and better prognosis (IDHmut-non-codel and IDHmut-codel subtypes) (all p < 0.05) in LGG. Kaplan-Meier survival curves from three databases showed that high NCOA4-expressing LGG patients had better prognosis (all p < 0.05). NCOA4 correlated weakly with B cells, CD8 + T cells, macrophages, and dendritic cells infiltration (all with correlation coefficients r < 0.3, and p < 0.05) in LGG. Multivariate Cox regression identified NCOA4, age, CD8 T cells, and macrophages as LGG independent prognostic factors (all p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that NCOA4’s primary function in LGG is related to autophagy processes (all p < 0.05). Conclusion Our findings suggest that NCOA4 could be a potential prognostic marker and therapeutic target in LGG.
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spelling doaj-art-a5be9be106ca4e5db606eabd4f760cda2025-01-19T12:28:08ZengBMCBMC Neurology1471-23772025-01-0125111310.1186/s12883-025-04036-4Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validationGuangtang Chen0Xueping Shi1Rukai Jiao2Jiacai Qian3Xiaolin Du4Jian Liu5Xi Zeng6Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical UniversityDepartment of Neurosurgery, The Affiliated Jinyang Hospital of Guizhou Medical UniversityDepartment of Neurosurgery, The Affiliated Jinyang Hospital of Guizhou Medical UniversityDepartment of Neurosurgery, The Affiliated Jinyang Hospital of Guizhou Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical UniversityAbstract Background Low-grade glioma (LGG) is a primary brain tumor with relatively low malignancy. NCOA4 is a key regulator of ferritinophagy-related processes and is involved in the occurrence and development of many cancers. However, the role of NCOA4 in LGG remains poorly understood. Methods This study comprehensively analyzed several mainstream bioinformatics databases to explore the expression, diagnostic efficacy, clinical pathological features, immune infiltration, prognostic value, and biological functions of NCOA4 in LGG. Immunohistochemistry experiments were conducted using LGG tissue samples collected from our hospital to validate the bioinformatics analysis results. Results NCOA4 expression was significantly elevated in LGG (p < 0.05), with an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.973, suggesting it as a potential diagnostic marker. High NCOA4 expression was associated with younger age (21–40 years), lower malignancy (oligodendroglioma), and better prognosis (IDHmut-non-codel and IDHmut-codel subtypes) (all p < 0.05) in LGG. Kaplan-Meier survival curves from three databases showed that high NCOA4-expressing LGG patients had better prognosis (all p < 0.05). NCOA4 correlated weakly with B cells, CD8 + T cells, macrophages, and dendritic cells infiltration (all with correlation coefficients r < 0.3, and p < 0.05) in LGG. Multivariate Cox regression identified NCOA4, age, CD8 T cells, and macrophages as LGG independent prognostic factors (all p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that NCOA4’s primary function in LGG is related to autophagy processes (all p < 0.05). Conclusion Our findings suggest that NCOA4 could be a potential prognostic marker and therapeutic target in LGG.https://doi.org/10.1186/s12883-025-04036-4Low-grade gliomaNCOA4FerroptosisPrognosisBiomarker
spellingShingle Guangtang Chen
Xueping Shi
Rukai Jiao
Jiacai Qian
Xiaolin Du
Jian Liu
Xi Zeng
Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validation
BMC Neurology
Low-grade glioma
NCOA4
Ferroptosis
Prognosis
Biomarker
title Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validation
title_full Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validation
title_fullStr Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validation
title_full_unstemmed Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validation
title_short Expression and prognostic value of ferritinophagy-related NCOA4 gene in low-grade glioma: integration of bioinformatics and experimental validation
title_sort expression and prognostic value of ferritinophagy related ncoa4 gene in low grade glioma integration of bioinformatics and experimental validation
topic Low-grade glioma
NCOA4
Ferroptosis
Prognosis
Biomarker
url https://doi.org/10.1186/s12883-025-04036-4
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