肌萎缩侧索硬化液体生物标志物与临床特征的相关性

Correlation between fluid biomarkers and clinical features in amyotrophic lateral sclerosis

摘要:

目的 探讨肌萎缩侧索硬化（ALS）液体生物标志物与临床特征之间的相关性。方法 2019年1月至2023年2月十堰市人民医院神经内科前瞻性招募了27例ALS患者（ALS组）以及28例无中枢神经系统疾病的志愿者（对照组）。采用夹心酶联免疫吸附分析检测血浆及脑脊液（CSF）中的血管内皮生长因子（VEGF）、VEGF受体2（VEGFR2）、视神经蛋白（OPTN）、反式激活反应DNA结合蛋白43（TDP-43）、血管生成素（ANG）和单核细胞趋化蛋白-1（MCP-1）水平。在采集样本时收集患者临床资料。比较2组受试者的临床特征和液体生物标志物的差异。结果 ALS组患者的血浆及CSF中VEGF、VEGFR2、OPTN、TDP-43和ANG均低于对照组（P<0.05），而MCP-1高于对照组（P<0.05）。通过单变量线性回归分析及校正后，ALS患者的血浆VEGF与疾病进展率呈负相关（P<0.05），血浆VEGF、VEGFR2、OPTN与修订版ALS功能评定量表（ALSFRS-R）评分呈正相关（P<0.05）；同时，CSF中VEGF也与疾病进展率呈负相关（P<0.05），CSF中VEGF、VEGFR2与ALSFRS-R评分呈正相关（P<0.05）。经校正后则显示，血浆ANG与疾病进展率呈负相关（P<0.05）。通过单变量线性回归分析及校正后，ALS患者的血浆及CSF中TDP-43均与年龄呈正相关（P<0.05），ALS患者的血浆MCP-1与疾病进展率呈正相关（P<0.05），与ALSFRS-R评分呈负相关（P<0.05）；单变量回归分析显示，CSF中MCP-1也与疾病进展率呈正相关（P<0.05）。经斯皮尔曼秩相关性分析，血浆生物标志物间均呈正相关（P<0.05）；CSF生物标志物中VEGF与VEGFR2呈正相关（P<0.05），TDP-43与其他标志物呈正相关（P<0.05）。结论 6种液体生物标志物与ALS患者的年龄、疾病严重程度以及疾病进展相关。

Abstract:

Objective To investigate the correlation between fluid biomarkers and clinical features in amyotrophic lateral sclerosis （ALS）.Methods A total of 27 ALS patients who were treated in Shiyan People’s Hospital from January 2019 to February 2023 were enrolled as ALS group， and 28 volunteers without central nervous system disorders were enrolled as control group. Sandwich ELISA was used to measure the levels of vascular endothelial growth factor （VEGF）， VEGF receptor 2 （VEGFR2）， optineurin （OPTN）， TAR DNA-binding protein 43 （TDP-43）， angiopoietin （ANG）， and monocyte chemoattractant protein 1 （MCP-1） in plasma and cerebrospinal fluid （CSF）. Related clinical data were collected at the time of sample collection， and clinical features and fluid biomarkers were compared between the two groups.Results Compared with the control group， the ALS group had significantly lower levels of VEGF， VEGFR2， OPTN， TDP-43， and ANG and a significantly higher level of MCP-1 in plasma and CSF （P<0.05）. After univariate linear regression analysis and correction， plasma VEGF was negatively correlated with disease progression rate （P<0.05）， and plasma VEGF， VEGFR2， and OPTN were positively correlated with the score of ALS Functional Rating Scale-Revised （ALSFRS-R） （P<0.05）； in addition， VEGF in CSF was negatively correlated with disease progression rate （P<0.05）， and VEGF and VEGFR2 in CSF were positively correlated with ALSFRS-R score （P <0.05）. After correction， plasma ANG was negatively correlated with disease progression rate （P<0.05）. After univariate linear regression analysis and correction， TDP-43 in plasma and CSF was positively correlated with age in ALS patients （P<0.05）， and plasma MCP-1 was positively correlated with disease progression rate and was negatively correlated with ALSFRS-R score （P<0.05）； the univariate regression analysis showed that MCP-1 in CSF was also positively correlated with disease progression rate （P<0.05）. The Spearman rank correlation analysis showed positive correlations between plasma biomarkers （P<0.05）； as for the CSF biomarkers， VEGF was positively correlated with VEGFR2 （P <0.05）， and TDP-43 was positively correlated with other biomarkers （P<0.05）.Conclusions Six fluid biomarkers are associated with age， disease severity， and disease progression in ALS patients.