Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets
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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-02-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-89390-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850197246537105408 |
|---|---|
| author | Dai Shi Jingxuan Li Zhenpeng Niu Likun Wang Siying Ren Wen Gu Hui Yang Hong Xue Guofeng Wu |
| author_facet | Dai Shi Jingxuan Li Zhenpeng Niu Likun Wang Siying Ren Wen Gu Hui Yang Hong Xue Guofeng Wu |
| author_sort | Dai Shi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f8d7ece14b0e462f9cf7a5dcb56189dc |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-f8d7ece14b0e462f9cf7a5dcb56189dc2025-08-20T02:13:14ZengNature PortfolioScientific Reports2045-23222025-02-0115111610.1038/s41598-025-89390-6Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targetsDai Shi0Jingxuan Li1Zhenpeng Niu2Likun Wang3Siying Ren4Wen Gu5Hui Yang6Hong Xue7Guofeng Wu8School of Basic Medicine, Guizhou Medical UniversitySchool of Clinical Medicine, Guizhou Medical UniversitySchool of Basic Medicine, Guizhou Medical UniversityEmergency Department, Affiliated Hospital of Guizhou Medical UniversityEmergency Department, Affiliated Hospital of Guizhou Medical UniversityDepartment of Endocrinology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineDepartment of Neurology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineDepartment of Neurology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineSchool of Basic Medicine, Guizhou Medical UniversityAbstract 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.https://doi.org/10.1038/s41598-025-89390-6Temporal lobe epilepsyFerroptosis-related genesBiomarkersImmune cell infiltrationBioinformatics |
| spellingShingle | Dai Shi Jingxuan Li Zhenpeng Niu Likun Wang Siying Ren Wen Gu Hui Yang Hong Xue Guofeng Wu Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets Scientific Reports Temporal lobe epilepsy Ferroptosis-related genes Biomarkers Immune cell infiltration Bioinformatics |
| title | Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets |
| title_full | Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets |
| title_fullStr | Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets |
| title_full_unstemmed | Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets |
| title_short | Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets |
| title_sort | identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets |
| topic | Temporal lobe epilepsy Ferroptosis-related genes Biomarkers Immune cell infiltration Bioinformatics |
| url | https://doi.org/10.1038/s41598-025-89390-6 |
| work_keys_str_mv | AT daishi identificationandvalidationofdiagnosticbiomarkersfortemporallobeepilepsyrelatedtoferroptosisandpotentialtherapeutictargets AT jingxuanli identificationandvalidationofdiagnosticbiomarkersfortemporallobeepilepsyrelatedtoferroptosisandpotentialtherapeutictargets AT zhenpengniu identificationandvalidationofdiagnosticbiomarkersfortemporallobeepilepsyrelatedtoferroptosisandpotentialtherapeutictargets AT likunwang identificationandvalidationofdiagnosticbiomarkersfortemporallobeepilepsyrelatedtoferroptosisandpotentialtherapeutictargets AT siyingren identificationandvalidationofdiagnosticbiomarkersfortemporallobeepilepsyrelatedtoferroptosisandpotentialtherapeutictargets AT wengu identificationandvalidationofdiagnosticbiomarkersfortemporallobeepilepsyrelatedtoferroptosisandpotentialtherapeutictargets AT huiyang identificationandvalidationofdiagnosticbiomarkersfortemporallobeepilepsyrelatedtoferroptosisandpotentialtherapeutictargets AT hongxue identificationandvalidationofdiagnosticbiomarkersfortemporallobeepilepsyrelatedtoferroptosisandpotentialtherapeutictargets AT guofengwu identificationandvalidationofdiagnosticbiomarkersfortemporallobeepilepsyrelatedtoferroptosisandpotentialtherapeutictargets |