Cerebrospinal fluid quantitative proteomic reveals potential mechanisms and biomarker candidates of children with bacterial meningitis complicated by neurological complications

作者：Binglin Jian, Jing Wei, Liang Zhu, Lingyun Guo, Bing Hu, Yue Xie, Tianming Chen, Bing Liu, Wanrong Li, Juan Du, Linlin Liu, Xixi Zhang, Wei Sun, Zhengguang Guo, Kaihu Yao, Lulu Jia, Gang Liu · 发表于：Clinical Proteomics · 年份：2025 · DOI：10.1186/s12014-025-09548-2 · 被引用次数：2 · 研究领域：Bacterial Infections and Vaccines、Advanced Proteomics Techniques and Applications、Pneumonia and Respiratory Infections

BACKGROUND: Bacterial meningitis complicated by neurological complications (BMN) is a major cause of poor outcomes and mortality among children with bacterial meningitis. So far, the host-related mechanisms and diagnostic biomarkers of BMN and bacterial meningitis without neurological complications (BM) remain poorly understood and limited. METHODS: We implemented a two-stage cerebrospinal fluid (CSF) quantitative proteomics study involving three groups: children with BMN, BM, and diseases not involving the central nervous system(Ctrl). Initially, in the discovery cohort, data-independent acquisition (DIA) mass spectrometry was used for proteomic profiling on 242 CSF samples (77 BMN, 52 BM, and 113 Ctrl). Differentially expressed proteins (DEPs) were identified among the BMN/Ctrl, BM/Ctrl, and BMN/BM groups, followed by an analysis of their functional enrichment. Next, the parallel reaction monitoring (PRM) method was used to validate the essential DEPs identified during the DIA phase in a validation cohort of 196 subjects (94 BMN, 47 BM, and 55 Ctrl). Subsequently, the validated DEPs were further filtered to construct a PRM-based machine learning model that distinguishes between BMN and BM. RESULTS: A total of 1376 DEPs were identified in BM/Ctrl (757 upregulated, 619 downregulated), 1295 in BMN/Ctrl (745 upregulated, 550 downregulated), and 356 in BMN/BM(60 upregulated, 296 downregulated), respectively. The functional results indicate that the upregulated DEPs were primaril...