Integrated landscape of plasma metabolism and proteome of patients with post-traumatic deep vein thrombosis
Kun Zhang, Pengfei Wang, Wei Huang, Shi-Hao Tang, Hanzhong Xue, Hao Wu, Ying Zhang, Yu Rong, Shan‐Shan Dong, Jiabin Chen, Yan Zou, Tian Ding, Na Yang, Yifan Liang, Liu Chungui, Dongyang Li, Kun Zhang, Tie‐Lin Yang, Yan Guo
Abstract
Deep vein thrombosis (DVT) is a leading cause of morbidity and mortality after trauma. Here, we integrate plasma metabolomics and proteomics to evaluate the metabolic alterations and their function in up to 680 individuals with and without DVT after trauma (pt-DVT). We identify 28 metabolites and 2 clinical parameter clusters associated with pt-DVT. Then, we develop a panel of 9 metabolites (hexadecanedioic acid, pyruvic acid, L-Carnitine, serotonin, PE(P-18:1(11Z)/18:2(9Z,12Z)), 3-Hydroxycapric acid, 5,6-DHET, 3-Methoxybenzenepropanoic acid and pentanenitrile) that can predict pt-DVT with high performance, which can be verified in an independent cohort. Furthermore, the integration analysis of metabolomics and proteomics data indicates that the upregulation of glycolysis/gluconeogenesis-TCA cycle may promote thrombosis by regulating ROS levels in red blood cells, suggesting that interfering with this process might be potential therapeutic strategies for pt-DVT. Together, our study comprehensively delineates the metabolic and hematological dysregulations for pt-DVT, and provides potential biomarkers for early detection. Deep vein thrombosis after trauma (pt-DVT) patients undergo metabolic changes but a comprehensive characterization in humans is lacking. Here the authors integrate metabolome and proteome to reveal pt-DVT-related metabolic alterations and their function, and reveal potential biomarkers.