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已发表论文
重症监护病房患者脓毒症诊断及预后的前降钙素原、人附睾蛋白 4 和氧合指数联合生物标志物检测组合
Authors Luo J, An S, Liao X, Wu J, Li L
Received 11 May 2025
Accepted for publication 25 September 2025
Published 10 October 2025 Volume 2025:18 Pages 14147—14159
DOI https://doi.org/10.2147/JIR.S539733
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Anh Ngo
Jinmei Luo,1,* Shu An,2,* Xuanren Liao,2,* Juehui Wu,2 Laisheng Li2
1Department of Medical Intensive Care Unit, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 2Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Juehui Wu, Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road, Guangzhou, 510080, People’s Republic of China, Tel/Fax +86-20-28823350-8464, Email wujh98@mail.sysu.edu.cn Laisheng Li, Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road, Guangzhou, 510080, People’s Republic of China, Tel/Fax +86-20-28823350-8464, Email lilaish@mail.sysu.edu.cn
Background: Sepsis remains a lethal global health crisis with persistently high mortality, exacerbated by diagnostic challenges stemming from its heterogeneous clinical presentation and limitations of current diagnostic tools like SOFA score. While biomarkers such as Presepsin or human epididymis protein 4 (HE4) show promise, single-marker approaches exhibit insufficient accuracy for reliable early detection and prognosis.
Objective: We evaluated the diagnostic and prognostic utility of Presepsin, HE4, Oxygenation Index (OI), and their combined panel (PHO) in critically ill patients with or without sepsis.
Methods: This single-center study analyzed 411 ICU patients (165 non-sepsis, 246 sepsis or septic shock). Clinical parameters—including SOFA, and OI—alongside laboratory parameters (hematological indices, hepatic/renal function markers, inflammatory biomarkers, blood culture results) were extracted from the hospital’s Laboratory Information System. Residual admission samples were used to quantify Presepsin and HE4. Receiver operating characteristic (ROC) curve analysis, Spearman’s rank correlation, and gradient boosting machine learning models were employed to evaluate the diagnostic and prognostic performance.
Results: Presepsin, HE4, and OI were significantly elevated in septic patients compared to controls (all P < 0.05) and correlated strongly with 30-day mortality. The gradient boosting algorithm identified these three markers as the most significant predictors. Importantly, the combined biomarker panel PHO demonstrated superior performance in both diagnosis and prognosis. For sepsis diagnosis, PHO achieved an outstanding AUC of 0.892 (95% CI: 0.860– 0.924), significantly outperforming individual biomarkers (Presepsin: 0.821; HE4: 0.803; OI: 0.752) and conventional inflammatory markers (all P< 0.05). For mortality prediction, PHO maintained the highest prognostic accuracy (AUC 0.706, 95% CI: 0.641– 0.772), with improved sensitivity and specificity compared to single biomarkers.
Conclusion: The combined Presepsin, HE4 and OI biomarker panel significantly outperforms individual markers in sepsis diagnosis and prognosis. This machine learning-validated composite indicator enables early risk stratification and may guide timely interventions to improve outcomes.
Keywords: presepsin, HE4, oxygenation index, sepsis, diagnosis, prognosis
1Department of Medical Intensive Care Unit, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 2Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Juehui Wu, Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road, Guangzhou, 510080, People’s Republic of China, Tel/Fax +86-20-28823350-8464, Email wujh98@mail.sysu.edu.cn Laisheng Li, Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road, Guangzhou, 510080, People’s Republic of China, Tel/Fax +86-20-28823350-8464, Email lilaish@mail.sysu.edu.cn
Background: Sepsis remains a lethal global health crisis with persistently high mortality, exacerbated by diagnostic challenges stemming from its heterogeneous clinical presentation and limitations of current diagnostic tools like SOFA score. While biomarkers such as Presepsin or human epididymis protein 4 (HE4) show promise, single-marker approaches exhibit insufficient accuracy for reliable early detection and prognosis.
Objective: We evaluated the diagnostic and prognostic utility of Presepsin, HE4, Oxygenation Index (OI), and their combined panel (PHO) in critically ill patients with or without sepsis.
Methods: This single-center study analyzed 411 ICU patients (165 non-sepsis, 246 sepsis or septic shock). Clinical parameters—including SOFA, and OI—alongside laboratory parameters (hematological indices, hepatic/renal function markers, inflammatory biomarkers, blood culture results) were extracted from the hospital’s Laboratory Information System. Residual admission samples were used to quantify Presepsin and HE4. Receiver operating characteristic (ROC) curve analysis, Spearman’s rank correlation, and gradient boosting machine learning models were employed to evaluate the diagnostic and prognostic performance.
Results: Presepsin, HE4, and OI were significantly elevated in septic patients compared to controls (all P < 0.05) and correlated strongly with 30-day mortality. The gradient boosting algorithm identified these three markers as the most significant predictors. Importantly, the combined biomarker panel PHO demonstrated superior performance in both diagnosis and prognosis. For sepsis diagnosis, PHO achieved an outstanding AUC of 0.892 (95% CI: 0.860– 0.924), significantly outperforming individual biomarkers (Presepsin: 0.821; HE4: 0.803; OI: 0.752) and conventional inflammatory markers (all P< 0.05). For mortality prediction, PHO maintained the highest prognostic accuracy (AUC 0.706, 95% CI: 0.641– 0.772), with improved sensitivity and specificity compared to single biomarkers.
Conclusion: The combined Presepsin, HE4 and OI biomarker panel significantly outperforms individual markers in sepsis diagnosis and prognosis. This machine learning-validated composite indicator enables early risk stratification and may guide timely interventions to improve outcomes.
Keywords: presepsin, HE4, oxygenation index, sepsis, diagnosis, prognosis