Circulating proteomic biomarkers for diagnosing sporadic amyotrophic lateral sclerosis:a cross-sectional study  

作　　者：Lu He Qinming Zhou Chaoyang Xiu Yaping Shao Dingding Shen Huanyu Meng Weidong Le Sheng Chen 

机构地区：[1]Department of Neurology and Institute of Neurology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [2]Department of Neurology,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan Province,China [3]Center for Translational Research on Neurological Diseases,the First Affiliated Hospital,Dalian Medical University,Dalian,Liaoning Province,China [4]Co-innovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu Province,China [5]Institute of Neurology,Sichuan Academy of Medical Sciences-Sichuan Provincial Hospital,Chengdu,Sichuan Province,China [6]Department of Neurology,Xinrui Hospital,Wuxi,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2024年第8期1842-1848,共7页中国神经再生研究（英文版）

基　　金：supported by the grants from Shanghai Shuguang Plan Project,No.18SG15(to SC);Shanghai Outstanding Young Scholars Project;Shanghai Talent Development Project,No.2019044(to SC);Medical-engineering cross fund of Shanghai Jiao Tong University,No.YG2022QN009(to QZ);the National Natural Science Foundation of China,No.82201558(to QZ)。

摘　　要：Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively d

关 键 词：amyotrophic lateral sclerosis cathelicidin-related antimicrobial peptide HEMOGLOBIN label-free quantitative proteomics multi-protein combined diagnostic panel serum biomarkers talin-1 translationally-controlled tumor protein ZYXIN 

分 类 号：R744.8[医药卫生—神经病学与精神病学]