个体的急性脊髓损伤与创伤对照的特定血液 RNA 谱。

Specific Blood RNA Profiles in Individuals with Acute Spinal Cord Injury as Compared with Trauma Controls.

机构信息

Spine Center, Department of Orthopaedics, Shanghai Changzheng Hospital, Second Affiliated Hospital of Naval Medical University, Shanghai, China.

Department of Orthopaedics, No. 905 Hospital of PLA Navy, Shanghai, China.

出版信息

Oxid Med Cell Longev. 2023 Jan 12;2023:1485135. doi: 10.1155/2023/1485135. eCollection 2023.

DOI:10.1155/2023/1485135

PMID:36686379

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9851797/

Abstract

BACKGROUND

Spinal cord injury (SCI) is known to cause a more robust systemic inflammatory response than general trauma without CNS injury, inducing severe secondary organ damage, especially the lung and liver. Related studies are principally focused on the mechanisms underlying repair and regeneration in the injured spinal cord tissue. However, the specific mechanism of secondary injury after acute SCI is widely overlooked, compared with general trauma.

METHODS

Two datasets of GSE151371 and GSE45376 related to the blood samples and spinal cord after acute SCI were selected to identify the differentially expressed genes (DEGs). In GSE151371, functional enrichment analysis on specific DEGs of blood samples was performed. And the top 15 specific hub genes were identified from intersectional genes between the specific upregulated DEGs of blood samples in GSE151371 and the upregulated DEGs of the spinal cord in GSE45376. The specific functional enrichment analysis and the drug candidates of the hub genes and the miRNAs-targeted hub genes were also analyzed and predicted.

RESULTS

DEGs were identified, and a total of 64 specific genes were the intersection of upregulated genes of the spinal cord in GSE45376 and upregulated genes of human blood samples in GSE151371. The top 15 hub genes including HP, LCN2, DLGAP5, CEP55, HMMR, CDKN3, PRTN3, SKA3, MPO, LTF, CDC25C, MMP9, NEIL3, NUSAP1, and CD163 were calculated from the 64 specific genes. Functional enrichment analysis of the top 15 hub genes revealed inflammation-related pathways. The predicted miRNAs-targeted hub genes and drug candidates of hub genes were also performed to put forward reasonable treatment strategies.

CONCLUSION

The specific hub genes of acute SCI as compared with trauma without CNS injury were identified. The functional enrichment analysis of hub genes showed a specific immune response. Several predicted drugs of hub genes were also obtained. The hub genes and the predicted miRNAs may be potential biomarkers and therapeutic targets and require further validation.

摘要

背景

脊髓损伤（SCI）比无中枢神经系统损伤的一般创伤引起更强的全身炎症反应，导致严重的继发性器官损伤，特别是肺和肝。相关研究主要集中在损伤脊髓组织的修复和再生机制上。然而，与一般创伤相比，急性 SCI 后继发性损伤的具体机制广泛被忽视。

方法

选择与急性 SCI 后血液样本和脊髓相关的两个数据集 GSE151371 和 GSE45376 来识别差异表达基因（DEGs）。在 GSE151371 中，对血液样本中特定 DEGs 进行功能富集分析。并从 GSE151371 中血液样本特定上调 DEGs 与 GSE45376 中脊髓上调 DEGs 的交集基因中鉴定出前 15 个特定的 hub 基因。还分析和预测了 hub 基因和靶向 hub 基因的 miRNA 的特定功能富集分析和药物候选物。

结果

鉴定出 DEGs，共有 64 个特定基因是 GSE45376 中脊髓上调基因和 GSE151371 中人类血液样本上调基因的交集。从 64 个特定基因中计算出前 15 个 hub 基因，包括 HP、LCN2、DLGAP5、CEP55、HMMR、CDKN3、PRTN3、SKA3、MPO、LTF、CDC25C、MMP9、NEIL3、NUSAP1 和 CD163。前 15 个 hub 基因的功能富集分析显示了与炎症相关的途径。还对 hub 基因的预测 miRNA 靶向 hub 基因和药物候选物进行了预测，提出了合理的治疗策略。