用于重症监护病房脓毒症患者诊断、鉴别诊断及短期死亡率的铁死亡相关蛋白质生物标志物

Ferroptosis-related protein biomarkers for diagnosis, differential diagnosis, and short-term mortality in patients with sepsis in the intensive care unit.

作者信息

Zeng Zhangrui, Deng Jie, Wang Gang, Luo Zixiang, Xiao Weijia, Xie Wenchao, Liu Jinbo, Li Ke

机构信息

Department of Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Core Research Laboratory, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.

出版信息

Front Immunol. 2025 Apr 8;16:1528986. doi: 10.3389/fimmu.2025.1528986. eCollection 2025.

BACKGROUND

Sepsis is a disease with high mortality caused by a dysregulated response to infection. Ferroptosis is a newly discovered type of cell death. Ferroptosis-related genes are involved in the occurrence and development of sepsis. However, research on the diagnostic value of ferroptosis-related protein biomarkers in sepsis serum is limited. This study aims to explore the clinical value of Ferroptosis-related proteins in diagnosing sepsis and predicting mortality risk.

METHODS

A single-center, prospective, observational study was conducted from January to December 2023, involving 170 sepsis patients, 49 non-septic ICU patients, and 50 healthy individuals. Upon ICU admission, biochemical parameters, GCS, SOFA, and APACHE II scores were recorded, and surplus serum was stored at -80°C for biomarker analysis via ELISA. Diagnostic efficacy was evaluated using ROC curve analysis.

RESULTS

Baseline serum levels of ACSL4, GPX4, PTGS2, CL-11, IL-6, IL-8, PCT, and hs-CRP significantly differed among sepsis, non-septic, and healthy individuals (all pvalue 0.01). ACSL4, GPX4, PTGS2, IL-6, IL-8, PCT, and hs-CRP demonstrated high diagnostic and differential diagnostic performance (AUC: 0.6688 to 0.9945). IL-10 and TNF-α showed good diagnostic performance (AUC = 0.8955 and 0.7657, respectively). ACSL4 (AUC = 0.7127) was associated with predicting sepsis mortality. Serum levels of ACSL4, CL-11, and IL-6 above the cut-off value were associated with shorter survival times. ACSL4 levels were positively correlated with SOFA (Rho = 0.354, pvalue < 0.0001), APACHE II (Rho = 0.317, pvalue < 0.0001), and septic shock (Rho = 0.274, pvalue = 0.003) scores but negatively correlated with the GCS score (Rho = -0.218, pvalue = 0.018). GPX4 levels were positively correlated with SOFA (Rho = 0.204, pvalue = 0.027) and APACHE II (Rho = 0.233, pvalue = 0.011) scores.

CONCLUSION

ACSL4 and GPX4 have strong diagnostic and differential diagnostic value in sepsis, including the ability to predict 28-day mortality in sepsis patients, and may become new potential serum markers for the diagnostic and differential diagnostic of sepsis.

背景

脓毒症是一种因对感染反应失调而导致高死亡率的疾病。铁死亡是一种新发现的细胞死亡类型。铁死亡相关基因参与脓毒症的发生发展。然而，关于铁死亡相关蛋白质生物标志物在脓毒症血清中的诊断价值的研究有限。本研究旨在探讨铁死亡相关蛋白在诊断脓毒症及预测死亡风险中的临床价值。

方法

于2023年1月至12月进行了一项单中心、前瞻性、观察性研究，纳入170例脓毒症患者、49例非脓毒症ICU患者和50例健康个体。入住ICU时，记录生化参数、格拉斯哥昏迷量表（GCS）、序贯器官衰竭评估（SOFA）和急性生理与慢性健康状况评分系统II（APACHE II）评分，并将剩余血清储存在-80°C用于通过酶联免疫吸附测定（ELISA）进行生物标志物分析。使用受试者工作特征（ROC）曲线分析评估诊断效能。

结果

脓毒症患者、非脓毒症患者和健康个体之间，酰基辅酶A合成酶长链家族成员4（ACSL4）、谷胱甘肽过氧化物酶4（GPX4）、前列腺素内过氧化物合酶2（PTGS2）、趋化素样因子11（CL-11）、白细胞介素6（IL-6）、白细胞介素8（IL-8）、降钙素原（PCT）和高敏C反应蛋白（hs-CRP）的基线血清水平存在显著差异（所有p值<0.01）。ACSL4、GPX4、PTGS2、IL-6、IL-8、PCT和hs-CRP表现出较高的诊断和鉴别诊断性能（曲线下面积[AUC]：0.6688至0.9945）。白细胞介素10（IL-10）和肿瘤坏死因子-α（TNF-α）表现出良好的诊断性能（AUC分别为0.8955和0.7657）。ACSL4（AUC = 0.7127）与预测脓毒症死亡率相关。ACSL4、CL-11和IL-6的血清水平高于临界值与较短的生存时间相关。ACSL4水平与SOFA评分（斯皮尔曼相关系数Rho = 0.354，p值<0.0001）、APACHE II评分（Rho = 0.317，p值<0.0001）和感染性休克评分（Rho = 0.274，p值 = 0.003）呈正相关，但与GCS评分呈负相关（Rho = -0.218，p值 = 0.018）。GPX4水平与SOFA评分（Rho = 0.204，p值 = 0.027）和APACHE II评分（Rho = 0.233，p值 = 0.011）呈正相关。