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脊髓损伤中具有临床和生物学价值的细胞焦亡相关基因特征的综合分析

Comprehensive analysis of a pyroptosis-related gene signature of clinical and biological values in spinal cord injury.

作者信息

Zhang Pingping, Zhang Jianping, Kou Wenjuan, Gu Guangjin, Zhang Yaning, Shi Weihan, Chu Pengcheng, Liang Dachuan, Sun Guangwei, Shang Jun

机构信息

Department of Orthopedics, Seventh Affiliated Hospital of Shanxi Medical University, Linfen People's Hospital, Linfen, Shanxi, China.

Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China.

出版信息

Front Neurol. 2023 May 19;14:1141939. doi: 10.3389/fneur.2023.1141939. eCollection 2023.

Abstract

BACKGROUND

Since some of the clinical examinations are not suitable for patients with severe spinal cord injury (SCI), blood biomarkers have been reported to reflect the severity of SCI. The objective of this study was to screen out the potential biomarkers associated with the diagnosis of SCI by bioinformatics analysis.

METHODS

The microarray expression profiles of SCI were obtained from the Gene Expression Omnibus (GEO) database. Core genes correlated to pyroptosis were obtained by crossing the differential genes, and module genes were obtained by WGCNA analysis and lasso regression. The immune infiltration analysis and GSEA analysis revealed the essential effect of immune cells in the progression of SCI. In addition, the accuracy of the biomarkers in diagnosing SCI was subsequently evaluated and verified using the receiver operating characteristic curve (ROC) and qRT-PCR.

RESULTS

A total of 423 DEGs were identified, among which 319 genes were upregulated and 104 genes were downregulated. Based on the WGCNA analysis, six potential biomarkers were screened out, including LIN7A, FCGR1A, FGD4, GPR27, BLOC1S1, and GALNT4. The results of ROC curves demonstrated the accurate value of biomarkers related to SCI. The immune infiltration analysis and GSEA analysis revealed the essential effect of immune cells in the progression of SCI, including macrophages, natural killer cells, and neutrophils. The qRT-PCR results verified that FGD4, FCAR1A, LIN7A, BLOC1S1, and GPR27 were significantly upregulated in SCI patients.

CONCLUSION

In this study, we identified and verified five immune pyroptosis-related hub genes by WGCNA and biological experiments. It is expected that the five identified potential biomarkers in peripheral white blood cells may provide a novel strategy for early diagnosis.

摘要

背景

由于一些临床检查不适用于严重脊髓损伤(SCI)患者,据报道血液生物标志物可反映SCI的严重程度。本研究的目的是通过生物信息学分析筛选出与SCI诊断相关的潜在生物标志物。

方法

从基因表达综合数据库(GEO)中获取SCI的微阵列表达谱。通过交叉差异基因获得与细胞焦亡相关的核心基因,并通过加权基因共表达网络分析(WGCNA)和套索回归获得模块基因。免疫浸润分析和基因集富集分析(GSEA)揭示了免疫细胞在SCI进展中的重要作用。此外,随后使用受试者工作特征曲线(ROC)和qRT-PCR评估并验证了生物标志物在诊断SCI中的准确性。

结果

共鉴定出423个差异表达基因(DEG),其中319个基因上调,104个基因下调。基于WGCNA分析,筛选出6个潜在生物标志物,包括LIN7A、FCGR1A、FGD4、GPR27、BLOC1S1和GALNT4。ROC曲线结果证明了与SCI相关的生物标志物的准确价值。免疫浸润分析和GSEA分析揭示了免疫细胞在SCI进展中的重要作用,包括巨噬细胞、自然杀伤细胞和中性粒细胞。qRT-PCR结果证实,FGD4、FCAR1A、LIN7A、BLOC1S1和GPR27在SCI患者中显著上调。

结论

在本研究中,我们通过WGCNA和生物学实验鉴定并验证了5个与免疫细胞焦亡相关的枢纽基因。预期在外周血白细胞中鉴定出的这5个潜在生物标志物可能为早期诊断提供新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5862/10237016/1b455d48a499/fneur-14-1141939-g0001.jpg

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