Analysis of the value of potential biomarker S100-A8 protein in the diagnosis and pathogenesis of spinal tuberculosis

IF 3.4 3区医学 Q1 ORTHOPEDICS

JOR Spine Pub Date : 2024-04-10 DOI:10.1002/jsp2.1331

Zhibo Ren, Jinke Ji, Caili Lou, Yuxin Gao, Xueyan Feng, Qiang Ye, Wei Jia, Xu Zhang, Ningkui Niu

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Abstract

Objectives

The objective of this study is to evaluate the value of S100-A8 protein as a diagnostic marker for spinal tuberculosis and to explore its role in the potential pathogenesis of spinal tuberculosis (STB).

Methods

The peripheral blood of 100 spinal tuberculosis patients admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were collected as the observation group, and the peripheral blood of 30 healthy medical examiners were collected as the control group. Three samples from the observation group and three samples from the control group were selected for proteomics detection and screening of differential proteins. Kyoto Encyclopedia of Genes (KEGG) was used to enrich and analyze related signaling pathways to confirm the target protein. The serum expression levels of the target proteins were determined and compared between the two groups using enzyme-linked immunosorbent assay (ELISA). Statistical methods were used to evaluate the value of target protein as a diagnostic marker for STB. A macrophage model of Mycobacterium tuberculosis infection was constructed and S100-A8 small interfering RNA was used to investigate the molecular mechanism of the target protein.

Results

S100-A8 protein has the value of diagnosing spinal tuberculosis (AUC = 0.931, p < 0.001), and the expression level in the peripheral blood of the observation group (59.04 ± 19.37 ng/mL) was significantly higher than that of the control group (43.16 ± 10.07 ng/mL) (p < 0.05). S100-A8 protein expression showed a significant positive correlation with both CRP and ESR values (p < 0.01). Its AUCs for combined bacteriological detection, T-SPOT results, diagnostic imaging, antacid staining results, and pathological results were 0.705 (p < 0.05), 0.754 (p < 0.01), 0.716 (p < 0.01), 0.656 (p < 0.05), and 0.681 (p < 0.01), respectively. Lack of S100-A8 leads to a significant decrease in the expression levels of TLR4 and IL-17A in infected macrophages.

Conclusion

S100-A8 protein is differentially expressed in the peripheral blood of patients with spinal tuberculosis and healthy individuals and may be a novel candidate biomarker for the diagnosis of spinal tuberculosis. The feedback loop on the S100-A8-TLR4-IL-17A axis may play an important role in the inflammatory mechanism of spinal tuberculosis.

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潜在生物标志物 S100-A8 蛋白在脊柱结核诊断和发病机制中的价值分析

摘要】目的评价S100-A8蛋白作为脊柱结核诊断标志物的价值，探讨其在脊柱结核（STB）潜在发病机制中的作用。方法采集2018年9月至2021年6月宁夏医科大学总医院收治的100例脊柱结核患者外周血作为观察组，采集30例健康体检者外周血作为对照组。选取观察组和对照组各3份样本进行蛋白质组学检测，筛选差异蛋白。利用京都基因百科全书（KEGG）对相关信号通路进行富集和分析，以确认目标蛋白。使用酶联免疫吸附试验（ELISA）测定并比较两组患者血清中目标蛋白的表达水平。采用统计方法评估靶蛋白作为 STB 诊断标志物的价值。构建了结核分枝杆菌感染的巨噬细胞模型，并使用 S100-A8 小干扰 RNA 研究了目标蛋白的分子机制。结果 S100-A8蛋白具有诊断脊柱结核的价值（AUC = 0.931，p <0.001），观察组外周血中的表达水平（59.04 ± 19.37 ng/mL）明显高于对照组（43.16 ± 10.07 ng/mL）（p <0.05）。S100-A8 蛋白表达与 CRP 和 ESR 值均呈显著正相关（p < 0.01）。其与细菌学检测、T-SPOT 结果、影像学诊断、抗酸染色结果和病理学结果的综合 AUC 分别为 0.705 (p < 0.05)、0.754 (p < 0.01)、0.716 (p < 0.01)、0.656 (p < 0.05) 和 0.681 (p < 0.01)。缺乏 S100-A8 会导致受感染巨噬细胞中 TLR4 和 IL-17A 的表达水平显著下降。结论 S100-A8 蛋白在脊柱结核患者和健康人外周血中的表达存在差异，可能是诊断脊柱结核的新型候选生物标志物。S100-A8-TLR4-IL-17A 轴的反馈回路可能在脊柱结核的炎症机制中发挥重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JOR Spine ORTHOPEDICS-

CiteScore

6.40

自引率

18.90%

发文量

审稿时长

10 weeks