Prognostic gene landscapes and therapeutic insights in sepsis-induced coagulopathy

作者全名：Ran, Xiaoli; Zhang, Jun; Wu, Yinyu; Du, Yunxia; Bao, Daiqin; Pei, Haoyu; Zhang, Yue; Zhou, Xiaoqiong; Li, Rui; Tang, Xu; She, Han; Mao, Qingxiang

作者地址：[Ran, Xiaoli; Zhang, Jun; Wu, Yinyu; Du, Yunxia; Bao, Daiqin; Pei, Haoyu; Zhou, Xiaoqiong; Li, Rui; She, Han; Mao, Qingxiang] Army Med Univ, Daping Hosp, Dept Anesthesiol, Chongqing 400042, Peoples R China; [Zhang, Yue] Army Med Univ, Daping Hosp, Dept Med Engn, Chongqing 400042, Peoples R China; [Tang, Xu] Chongqing Med Univ, Dept Anesthesiol, Affiliated Banan Hosp, Chongqing 400042, Peoples R China

通信作者：She, H; Mao, QX (通讯作者)，Army Med Univ, Daping Hosp, Dept Anesthesiol, Chongqing 400042, Peoples R China.; Tang, X (通讯作者)，Chongqing Med Univ, Dept Anesthesiol, Affiliated Banan Hosp, Chongqing 400042, Peoples R China.

来源：THROMBOSIS RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001214407800001

JCR分区：Q1

影响因子：3.7

年份：2024

卷号：237

期号：　

开始页：1

结束页：13

文献类型：Article

关键词：Sepsis -induced coagulopathy; Prognosis; Nomogram; Immune cell infiltration; Platelet activation

摘要：Background: Sepsis is a common and critical condition encountered in clinical practice that can lead to multiorgan dysfunction. Sepsis-induced coagulopathy (SIC) significantly affects patient outcomes. However, the precise mechanisms remain unclear, making the identification of effective prognostic and therapeutic targets imperative. Methods: The analysis of transcriptome data from the whole blood of sepsis patients, facilitated the identification of key genes implicated in coagulation. Then we developed a prognostic model and a nomogram to predict patient survival. Consensus clustering classified sepsis patients into three subgroups for comparative analysis of immune function and immune cell infiltration. Single-cell sequencing elucidated alterations in intercellular communication between platelets and immune cells in sepsis, as well as the role of the coagulation-related gene FYN. Real-time quantitative PCR determined the mRNA levels of critical coagulation genes in septic rats' blood. Finally, administration of a FYN agonist to septic rats was observed for its effects on coagulation functions and survival. Results: This study identified four pivotal genes-CFD, FYN, ITGAM, and VSIG4-as significant predictors of survival in patients with sepsis. Among them, CFD, FYN, and ITGAM were underexpressed, while VSIG4 was upregulated in patients with sepsis. Moreover, a nomogram that incorporates the coagulation-related genes (CoRGs) risk score with clinical features of patients accurately predicted survival probabilities. Subgroup analysis of CoRGs expression delineated three molecular sepsis subtypes, each with distinct prognoses and immune profiles. Single-cell sequencing shed light on heightened communication between platelets and monocytes, T cells, and plasmacytoid dendritic cells, alongside reduced interactions with neutrophils in sepsis. The collagen signaling pathway was found to be essential in this dynamic. FYN may affect platelet function by modulating factors such as ELF1, PTCRA, and RASGRP2. The administration of the FYN agonist can effectively improve coagulation dysfunction and survival in septic rats. Conclusions: The research identifies CoRGs as crucial prognostic markers for sepsis, highlighting the FYN gene's central role in coagulation disorders associated with the condition and suggesting novel therapeutic intervention strategies.

基金机构：National Natural Science Foundation of China [82300561]; General Program of Joint Medical Research of Chongqing Science and Health Commission and Chongqing Health Commission [2023MSXM127]; Natural Science Foundation of Chongqing [CSTB2023NSCQ-MSX0713]

基金资助正文：This study was supported by the National Natural Science Foundation of China (82300561) , General Program of Joint Medical Research of Chongqing Science and Health Commission and Chongqing Health Commission (2023MSXM127) and Natural Science Foundation of Chongqing (CSTB2023NSCQ-MSX0713) .