Bao Xiao-Hong, Chen Bao-Fu, Liu Jun, Tan Yu-Hua, Chen Shu, Zhang Fan, Lu Hong-Sheng, Li Ji-Cheng
Precision Medicine Center and Department of Cardiothoracic Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, China.
Medical Research Center, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan, China.
Front Mol Neurosci. 2023 May 24;16:1185021. doi: 10.3389/fnmol.2023.1185021. eCollection 2023.
Owing to the lack of valid biomarkers, the diagnosis of autism spectrum disorder (ASD) diagnosis relies solely on the behavioral phenotypes of children. Several researchers have suggested an association between ASD and inflammation; however, the complex relationship between the two is unelucidated to date. Therefore, the current study aims to comprehensively identify novel circulating ASD inflammatory biomarkers.
Olink proteomics was applied to compare the plasma inflammation-related protein changes in a group of the healthy children (HC, = 33) and another with ASD ( = 31). The areas under the receiver operating characteristic curves (AUCs) of the differentially expressed proteins (DEPs) were calculated. The functional analysis of the DEPs was performed using Gene Ontology and Kyoto Encyclopedia Genes and Genomes. Pearson correlation tests were used employed to analyze the correlation between the DEPs and clinical features.
A total of 13 DEPs were significantly up-regulated in the ASD group compared with the HC group. The four proteins, namely, STAMBP, ST1A1, SIRT2, and MMP-10 demonstrated good diagnostic accuracy with the corresponding AUCs (95% confidence interval, CI) of 0.7218 (0.5946-0.8489), 0.7107 (0.5827-0.8387), 0.7016 (0.5713-0.8319), and 0.7006 (0.568-0.8332). Each panel of STAMBP and any other differential protein demonstrated a better classification performance [AUC values from 0.7147 (0.5858-0.8436, STAMBP/AXIN1) to 0.7681 (0.6496-0.8867, STAMBP/MMP-10)]. These DEP profiles were enriched in immune and inflammatory response pathways, including TNF and NOD-like receptor signaling pathways. The interaction between STAMBP and SIRT2 ( = 0.97, = 8.52 × 10) was found to be the most significant. In addition, several DEPs related to clinical features in patients with ASD, particularly AXIN1 ( = 0.36, = 0.006), SIRT2 ( = 0.34, = 0.010) and STAMBP ( = 0.34, = 0.010), were positively correlated with age and parity, indicating that older age and higher parity may be the inflammation-related clinical factors in ASD.
Inflammation plays a crucial role in ASD, and the up-regulated inflammatory proteins may serve as potential early diagnostic biomarkers for ASD.
由于缺乏有效的生物标志物，自闭症谱系障碍（ASD）的诊断完全依赖于儿童的行为表型。一些研究人员提出ASD与炎症之间存在关联；然而，迄今为止两者之间的复杂关系尚未阐明。因此，本研究旨在全面鉴定新的循环ASD炎症生物标志物。
应用Olink蛋白质组学比较一组健康儿童（HC，n = 33）和另一组ASD儿童（n = 31）的血浆炎症相关蛋白变化。计算差异表达蛋白（DEP）的受试者工作特征曲线下面积（AUC）。使用基因本体论和京都基因与基因组百科全书对DEP进行功能分析。采用Pearson相关检验分析DEP与临床特征之间的相关性。
与HC组相比，ASD组共有13种DEP显著上调。四种蛋白质，即STAMBP、ST1A1、SIRT2和MMP-10表现出良好的诊断准确性，相应的AUC（95%置信区间CI）分别为0.7218（0.5946 - 0.8489）、0.7107（0.5827 - 0.8387）、0.7
