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pmid:39930056

Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets.

Dai Shi · Jingxuan Li · Zhenpeng Niu · Likun Wang · Siying Ren · Wen Gu · Hui Yang · Hong Xue · Guofeng Wu

Scientific reports · 2025 doi:10.1038/s41598-025-89390-6

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets.
doi
10.1038/s41598-025-89390-6
pmid
39930056
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[0]
Dai Shi
[1]
Jingxuan Li
[2]
Zhenpeng Niu
[3]
Likun Wang
[4]
Siying Ren
[5]
Wen Gu
[6]
Hui Yang
[7]
Hong Xue
[8]
Guofeng Wu
journal
Scientific reports
year
2025
abstract
Ferroptosis pathway activation is potentially correlated with temporal lobe epilepsy (TLE). However, the diagnostic significance and mechanism of ferroptosis-related genes (FRGs) in TLE require further investigation. A comprehensive analysis of the GSE134697 dataset from the Gene Expression Omnibus (GEO) database using Weighted gene co-expression network analysis (WGCNA) identified 3,212 differentially expressed genes (DEGs) between temporal lobe epilepsy (TLE) and control groups, with a critical focus on the turquoise module. Through intersection of DEGs and key module genes, correlation analyses with functional-related genes (FRG), protein-protein interactions (PPI), least absolute shrinkage and selection operator (LASSO), and machine learning methods, five potential biomarkers of ferroptosis (CBS, SHMT1, RIN3, QDPR, and PLPP4) were isolated. A nomogram was constructed using these markers, and enrichment analyses revealed their links to T-cell activation, allograft rejection, and glial differentiation. Variations in 13 immune cell types were also noted. Upregulation of CBS, RIN3, QDPR, and PLPP4 in TLE was confirmed through RT-qPCR and Western blot assays. Additionally, five SHMT1-targeting and one CBS-targeting drugs were predicted using the Drug-Gene Interaction Database (DGIdb). These findings provide new insights into the potential pathogenesis of TLE and suggest new targets for future research.
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To further analyze the association between the 437 candidate genes and TLE, five key genes were identified through 10-fold cross-validation using LASSO.
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To further analyze the association between the 437 candidate genes and TLE, five key genes were identified through 10-fold cross-validation using LASSO.
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The datasets analysed during the current study are available in the GSE134697 dataset (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE134697), FerrDb database (http://www.zhounan.org/ferrdb/current/), and BioGPS database (http://biogps.org/#goto=welcome).
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Through intersection of DEGs and key module genes, correlation analyses with functional-related genes (FRG), protein-protein interactions (PPI), least absolute shrinkage and selection operator (LASSO), and machine learning methods, five potential biomarkers of ferroptosis (CBS, SHMT1, RIN3, QDPR, and PLPP4) were isolated.
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Through intersection of DEGs and key module genes, correlation analyses with functional-related genes (FRG), protein-protein interactions (PPI), least absolute shrinkage and selection operator (LASSO), and machine learning methods, five potential biomarkers of ferroptosis (CBS, SHMT1, RIN3, QDPR, and PLPP4) were isolated.
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Through intersection of DEGs and key module genes, correlation analyses with functional-related genes (FRG), protein-protein interactions (PPI), least absolute shrinkage and selection operator (LASSO), and machine learning methods, five potential biomarkers of ferroptosis (CBS, SHMT1, RIN3, QDPR, and PLPP4) were isolated.
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However, the diagnostic significance and mechanism of ferroptosis-related genes (FRGs) in TLE require further investigation. A comprehensive analysis of the GSE134697 dataset from the Gene Expression Omnibus (GEO) database using Weighted gene co-expression network analysis (WGCNA) identified 3,212 differentially expressed genes (DEGs) between temporal lobe epilepsy (TLE) and control groups, with a critical focus on the turquoise module. Through intersection of DEGs and key module genes, correlation analyses with functional-related genes (FRG), protein-protein interactions (PPI), least absolute shrinkage and selection operator (LASSO), and machine learning methods, five potential biomarkers of ferroptosis (CBS, SHMT1, RIN3, QDPR, and PLPP4) were isolated. A nomogram was constructed using these markers, and enrichment analyses revealed their links to T-cell activation, allograft rejection, and glial differentiation. Variations in 13 immune cell types were also noted. Upregulation of CBS, RIN3, QDPR, and PLPP4 in TLE was confirmed through RT-qPCR and Western blot assays. Additionally, five SHMT1-targeting and one CBS-targeting drugs were predicted using the Drug-Gene Interaction Database (DGIdb). 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