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已发表论文
整合生物信息学鉴定出精神分裂症中 NLRP3 炎性小体枢纽基因及治疗靶点
Authors Ma J, Cui Y, Li X, Liu R, Wang J, Liu M , Kong L, Ren Y
Received 8 August 2025
Accepted for publication 24 November 2025
Published 1 December 2025 Volume 2025:21 Pages 2655—2670
DOI https://doi.org/10.2147/NDT.S555802
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Yu-Ping Ning
Jiawei Ma,1 Yongchun Cui,1 Xinying Li,2 Ruiyuan Liu,3 Jinhui Wang,3,4 Mengdi Liu,2 Linping Kong,5 Yan Ren6
1Department of Psychiatry, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China; 2School of Humanities and Social Sciences, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Academy of Medical Sciences, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4Department of Pharmacy, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 5Department of Medical Psychology, Taiyuan Psychiatric Hospital, Taiyuan, 030000, People’s Republic of China; 6Department of Psychiatry, The Fifth Hospital of Shanxi Medical University, The Fifth Clinical Medical College of Shanxi Medical University, Shanxi Provincial People’s Hospital, Taiyuan, 030012, People’s Republic of China
Correspondence: Yan Ren, Department of Psychiatry, The Fifth Hospital of Shanxi Medical University, The Fifth Clinical Medical College of Shanxi Medical University, Shanxi Provincial People’s Hospital, Taiyuan, 030012, People’s Republic of China, Email renyan_sxpph@sxmu.edu.cn
Background: The pathogenesis of schizophrenia (SZ) remains incompletely understood; although neuroinflammation and the NLRP3 inflammasome have been implicated, the key regulatory genes involved are still unidentified.
Objective: To investigate the association between SZ and NLRP3 inflammasome-related genes, and to screen for hub genes as potential biomarkers and therapeutic targets.
Methods: We analyzed the GEO dataset GSE27383, comprising 43 SZ patients and 29 controls, and identified 1,672 differentially expressed genes (DEGs). NLRP3-related genes were obtained from GeneCards, and weighted gene co-expression network analysis (WGCNA) highlighted the green, yellow, and red modules. The intersection of DEGs, NLRP3-related genes, and module genes was further refined using LASSO and Random Forest algorithms. Immune cell infiltration was profiled with CIBERSORT, and the diagnostic utility of candidate genes was evaluated using ROC curves. Molecular docking was performed to predict compound binding, and hub gene expression was validated in an independent cohort of 20 SZ patients and 20 controls using RT-qPCR on PBMCs.
Results: Five hub genes—HSPA8, SCAP, FLNA, TRAF2, and PINK1-AS—were significantly down-regulated in SZ (P < 0.05). The combined ROC-AUC reached 0.883. Molecular docking revealed strong binding affinities of ellagic acid to FLNA (− 4.70 kcal mol−1), and of hydralazine to HSPA8 (− 4.27), TRAF2 (− 4.84), and SCAP (− 4.98). Differential expression was confirmed in PBMCs. Additionally, SZ patients exhibited increased naive B cells and neutrophils, along with reduced resting NK cells and M2 macrophages.
Conclusion: Five genes (HSPA8, SCAP, FLNA, TRAF2, PINK1-AS) were identified as potential novel biomarkers and therapeutic targets for SZ, providing a theoretical foundation for elucidating disease mechanisms and advancing precision medicine in SZ.
Keywords: schizophrenia, NLRP3 inflammasome, molecular docking, bioinformatics, biomarkers, precision psychiatry
1Department of Psychiatry, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China; 2School of Humanities and Social Sciences, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Academy of Medical Sciences, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4Department of Pharmacy, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 5Department of Medical Psychology, Taiyuan Psychiatric Hospital, Taiyuan, 030000, People’s Republic of China; 6Department of Psychiatry, The Fifth Hospital of Shanxi Medical University, The Fifth Clinical Medical College of Shanxi Medical University, Shanxi Provincial People’s Hospital, Taiyuan, 030012, People’s Republic of China
Correspondence: Yan Ren, Department of Psychiatry, The Fifth Hospital of Shanxi Medical University, The Fifth Clinical Medical College of Shanxi Medical University, Shanxi Provincial People’s Hospital, Taiyuan, 030012, People’s Republic of China, Email renyan_sxpph@sxmu.edu.cn
Background: The pathogenesis of schizophrenia (SZ) remains incompletely understood; although neuroinflammation and the NLRP3 inflammasome have been implicated, the key regulatory genes involved are still unidentified.
Objective: To investigate the association between SZ and NLRP3 inflammasome-related genes, and to screen for hub genes as potential biomarkers and therapeutic targets.
Methods: We analyzed the GEO dataset GSE27383, comprising 43 SZ patients and 29 controls, and identified 1,672 differentially expressed genes (DEGs). NLRP3-related genes were obtained from GeneCards, and weighted gene co-expression network analysis (WGCNA) highlighted the green, yellow, and red modules. The intersection of DEGs, NLRP3-related genes, and module genes was further refined using LASSO and Random Forest algorithms. Immune cell infiltration was profiled with CIBERSORT, and the diagnostic utility of candidate genes was evaluated using ROC curves. Molecular docking was performed to predict compound binding, and hub gene expression was validated in an independent cohort of 20 SZ patients and 20 controls using RT-qPCR on PBMCs.
Results: Five hub genes—HSPA8, SCAP, FLNA, TRAF2, and PINK1-AS—were significantly down-regulated in SZ (P < 0.05). The combined ROC-AUC reached 0.883. Molecular docking revealed strong binding affinities of ellagic acid to FLNA (− 4.70 kcal mol−1), and of hydralazine to HSPA8 (− 4.27), TRAF2 (− 4.84), and SCAP (− 4.98). Differential expression was confirmed in PBMCs. Additionally, SZ patients exhibited increased naive B cells and neutrophils, along with reduced resting NK cells and M2 macrophages.
Conclusion: Five genes (HSPA8, SCAP, FLNA, TRAF2, PINK1-AS) were identified as potential novel biomarkers and therapeutic targets for SZ, providing a theoretical foundation for elucidating disease mechanisms and advancing precision medicine in SZ.
Keywords: schizophrenia, NLRP3 inflammasome, molecular docking, bioinformatics, biomarkers, precision psychiatry