Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration
BackgroundMajor depression disorder (MDD) is a devastating neuropsychiatric disease, and one of the leading causes of suicide. Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in numerous diseases. The study aimed to construct and validate a gene signature for diagno...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1215180/full |
| _version_ | 1827784672867778560 |
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| author | Jingjing Chen Xiaolong Jiang Xin Gao Wen Wu Zhengsheng Gu Ge Yin Rui Sun Jiasi Li Ruoru Wang Hailing Zhang Bingying Du Xiaoying Bi |
| author_facet | Jingjing Chen Xiaolong Jiang Xin Gao Wen Wu Zhengsheng Gu Ge Yin Rui Sun Jiasi Li Ruoru Wang Hailing Zhang Bingying Du Xiaoying Bi |
| author_sort | Jingjing Chen |
| collection | DOAJ |
| description | BackgroundMajor depression disorder (MDD) is a devastating neuropsychiatric disease, and one of the leading causes of suicide. Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in numerous diseases. The study aimed to construct and validate a gene signature for diagnosing MDD based on ferroptosis-related genes (FRGs) and further explore the biological functions of these genes in MDD.MethodsThe datasets were downloaded from the Gene Expression Omnibus (GEO) database and FRGs were obtained from the FerrDb database and other literatures. Least absolute shrinkage and selection operator (LASSO) regression and stepwise logistic regression were performed to develop a gene signature. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic power of the signature. Gene ontology (GO) enrichment analysis was used to explore the biological roles of these diagnostic genes, and single sample gene set enrichment analysis (ssGSEA) algorithm was used to evaluate immune infiltration in MDD. Animal model of depression was constructed to validate the expression of the key genes.ResultsEleven differentially expressed FRGs were identified in MDD patients compared with healthy controls. A signature of three FRGs (ALOX15B, RPLP0, and HP) was constructed for diagnosis of MDD. Afterwards, ROC analysis confirmed the signature’s discriminative capacity (AUC = 0.783, 95% CI = 0.719–0.848). GO enrichment analysis revealed that the differentially expressed genes (DEGs) related to these three FRGs were mainly involved in immune response. Furthermore, spearman correlation analysis demonstrated that these three FRGs were associated with infiltrating immune cells. ALOX15B and HP were significantly upregulated and RPLP0 was significantly downregulated in peripheral blood of the lipopolysaccharide (LPS)-induced depressive model.ConclusionOur results suggest that the novel FRG signature had a good diagnostic performance for MDD, and these three FRGs correlated with immune infiltration in MDD. |
| first_indexed | 2024-03-11T16:07:28Z |
| format | Article |
| id | doaj.art-952ded7c4f6842baa12da1ff3acd3c68 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-11T16:07:28Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-952ded7c4f6842baa12da1ff3acd3c682023-10-24T21:29:43ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-10-011010.3389/fmed.2023.12151801215180Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltrationJingjing Chen0Xiaolong Jiang1Xin Gao2Wen Wu3Zhengsheng Gu4Ge Yin5Rui Sun6Jiasi Li7Ruoru Wang8Hailing Zhang9Bingying Du10Xiaoying Bi11Department of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Laboratory Animal Sciences, School of Basic Medicine, Naval Medical University, Shanghai, ChinaDepartment of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaDepartment of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai, ChinaBackgroundMajor depression disorder (MDD) is a devastating neuropsychiatric disease, and one of the leading causes of suicide. Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in numerous diseases. The study aimed to construct and validate a gene signature for diagnosing MDD based on ferroptosis-related genes (FRGs) and further explore the biological functions of these genes in MDD.MethodsThe datasets were downloaded from the Gene Expression Omnibus (GEO) database and FRGs were obtained from the FerrDb database and other literatures. Least absolute shrinkage and selection operator (LASSO) regression and stepwise logistic regression were performed to develop a gene signature. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic power of the signature. Gene ontology (GO) enrichment analysis was used to explore the biological roles of these diagnostic genes, and single sample gene set enrichment analysis (ssGSEA) algorithm was used to evaluate immune infiltration in MDD. Animal model of depression was constructed to validate the expression of the key genes.ResultsEleven differentially expressed FRGs were identified in MDD patients compared with healthy controls. A signature of three FRGs (ALOX15B, RPLP0, and HP) was constructed for diagnosis of MDD. Afterwards, ROC analysis confirmed the signature’s discriminative capacity (AUC = 0.783, 95% CI = 0.719–0.848). GO enrichment analysis revealed that the differentially expressed genes (DEGs) related to these three FRGs were mainly involved in immune response. Furthermore, spearman correlation analysis demonstrated that these three FRGs were associated with infiltrating immune cells. ALOX15B and HP were significantly upregulated and RPLP0 was significantly downregulated in peripheral blood of the lipopolysaccharide (LPS)-induced depressive model.ConclusionOur results suggest that the novel FRG signature had a good diagnostic performance for MDD, and these three FRGs correlated with immune infiltration in MDD.https://www.frontiersin.org/articles/10.3389/fmed.2023.1215180/fullmajor depression disorderferroptosisimmune infiltrationGEO databasediagnostic biomarkers |
| spellingShingle | Jingjing Chen Xiaolong Jiang Xin Gao Wen Wu Zhengsheng Gu Ge Yin Rui Sun Jiasi Li Ruoru Wang Hailing Zhang Bingying Du Xiaoying Bi Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration Frontiers in Medicine major depression disorder ferroptosis immune infiltration GEO database diagnostic biomarkers |
| title | Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration |
| title_full | Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration |
| title_fullStr | Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration |
| title_full_unstemmed | Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration |
| title_short | Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration |
| title_sort | ferroptosis related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration |
| topic | major depression disorder ferroptosis immune infiltration GEO database diagnostic biomarkers |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1215180/full |
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