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鉴定与脊髓损伤严重程度相关的凝血诊断生物标志物。

Identification of coagulation diagnostic biomarkers related to the severity of spinal cord injury.

机构信息

Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China, 518107; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopedic Research Institute/Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China, 510080.

Linyi Central Hospital, Linyi, Shandong, China, 276000.

出版信息

Int Immunopharmacol. 2024 Aug 20;137:112505. doi: 10.1016/j.intimp.2024.112505. Epub 2024 Jun 21.

Abstract

BACKGROUND

Blood always shows coagulation changes after spinal cord injury (SCI), and identifying these blood changes may be helpful for diagnosis and treatment of SCI. Nevertheless, studies to date on blood coagulation changes after SCI in humans are not comprehensive. Therefore, this study aims to identify blood coagulation diagnostic biomarkers and immune changes related to SCI and its severity levels.

METHODS

Human blood sequencing datasets were obtained from public databases. Differentially expressed coagulation-related genes were analyzed (DECRGs). Enrichment analysis and assessment of immune changes were conducted. Weighted gene co-expression network analysis, least absolute shrinkage and selection operator logistic regression were used to identify biomarkers. Validation for these biomarkers was performed. The correlation between biomarkers and immune cells was evaluated. Transcription factors, miRNA, lncRNA, and drugs that can regulate biomarkers were analyzed.

RESULTS

DECRGs associated with SCI and its different grades were identified, showing enrichment in altered coagulation and immune-related signaling pathways. ADAM9, CD55, and STAT4 were identified as coagulation diagnostic biomarkers for SCI. IRF4 and PABPC4 were identified as coagulation diagnostic biomarkers for American Spinal Injury Association Impairment Scale (AIS) A grade of SCI. GP9 was designated as a diagnostic biomarker for AIS D grade of SCI. Immune changes in blood of SCI and its different grades were observed. Correlation between diagnostic biomarkers and immune cells were identified. Transcription factors, miRNA, lncRNA, and drugs that can regulate diagnostic biomarker expression were discovered.

CONCLUSION

Therefore, detecting the expression of these putative diagnostic biomarkers and related immune changes may be helpful for predicting the severity of SCI. Uncovering potential regulatory mechanisms for biomarkers may be beneficial for further research.

摘要

背景

脊髓损伤(SCI)后血液总会出现凝血变化,识别这些血液变化可能有助于 SCI 的诊断和治疗。然而,迄今为止,人类 SCI 后凝血变化的研究并不全面。因此,本研究旨在确定与 SCI 及其严重程度相关的凝血诊断生物标志物和免疫变化。

方法

从公共数据库中获取人类血液测序数据集。分析差异表达的凝血相关基因(DECRGs)。进行富集分析和免疫变化评估。使用加权基因共表达网络分析、最小绝对收缩和选择算子逻辑回归来识别生物标志物。对这些生物标志物进行验证。评估生物标志物与免疫细胞的相关性。分析可调节生物标志物的转录因子、miRNA、lncRNA 和药物。

结果

确定了与 SCI 及其不同等级相关的 DECRGs,这些基因在改变的凝血和免疫相关信号通路中显示出富集。ADAM9、CD55 和 STAT4 被鉴定为 SCI 的凝血诊断生物标志物。IRF4 和 PABPC4 被鉴定为 AIS A 级 SCI 的凝血诊断生物标志物。GP9 被指定为 AIS D 级 SCI 的诊断生物标志物。观察到 SCI 及其不同等级的血液免疫变化。确定了诊断生物标志物与免疫细胞之间的相关性。发现了可调节诊断生物标志物表达的转录因子、miRNA、lncRNA 和药物。

结论

因此,检测这些假定的诊断生物标志物和相关免疫变化的表达可能有助于预测 SCI 的严重程度。揭示生物标志物的潜在调节机制可能有助于进一步研究。

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