Yang Shaobo, Yang Hong, Huang Yanlei, Chen Gong, Shen Chun, Zheng Shan
Department of Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China.
J Proteome Res. 2023 Jul 7;22(7):2307-2318. doi: 10.1021/acs.jproteome.3c00008. Epub 2023 May 26.
Hirschsprung's disease (HSCR) is a congenital digestive tract malformation characterized by the absence of intramural ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract. Although the improvement of surgical methods has allowed great progress in the treatment of HSCR, its incidence and postoperative prognosis are still not ideal. The pathogenesis of HSCR remains unclear to date. In this study, metabolomic profiling of HSCR serum samples was performed by an integrated analysis of gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) as well as multivariate statistical analyses. Based on the random forest algorithm and receiver operator characteristic analysis, 21 biomarkers related to HSCR were optimized. Several amino acid metabolism pathways were identified as important disordered pathways of HSCR, among which tryptophan metabolism was crucial. To our knowledge, this is the first serum metabolomics study focusing on HSCR, and it provides a new perspective for explaining the mechanism of HSCR.
先天性巨结肠（HSCR）是一种先天性消化道畸形，其特征是沿胃肠道不同长度的肌间神经丛和黏膜下神经丛中缺乏壁内神经节细胞。尽管手术方法的改进使HSCR的治疗取得了很大进展，但其发病率和术后预后仍不理想。迄今为止，HSCR的发病机制仍不清楚。在本研究中，通过气相色谱-质谱联用（GC-MS）和液相色谱-高分辨率串联质谱联用（LC-HRMS/MS）的综合分析以及多变量统计分析，对HSCR血清样本进行了代谢组学分析。基于随机森林算法和受试者工作特征分析，优化了21种与HSCR相关的生物标志物。几种氨基酸代谢途径被确定为HSCR的重要紊乱途径，其中色氨酸代谢至关重要。据我们所知，这是第一项聚焦于HSCR的血清代谢组学研究，为解释HSCR的发病机制提供了新的视角。
