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ORIGINAL RESEARCH article

Front. Med.
Sec. Infectious Diseases: Pathogenesis and Therapy
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1505882
This article is part of the Research Topic Advancements in Sepsis Diagnosis Utilizing Next-Generation Sequencing Approaches for Personalized Medicine View all 4 articles

Plasma EphA2 Level is a Superior Biomarker to Del-1 for Sepsis Diagnosis and Prognosis

Provisionally accepted
Eun Hye LEE Eun Hye LEE Mi Hwa Shin Mi Hwa Shin Se Hyun Kwak Se Hyun Kwak Ji Soo Choi Ji Soo Choi Ah Young Leem Ah Young Leem Su Hwan Lee Su Hwan Lee Kyung Soo Chung Kyung Soo Chung YOUNG SAM KIM YOUNG SAM KIM Sang-Guk Lee Sang-Guk Lee Moo Suk Park Moo Suk Park *
  • College of Medicine, Yonsei University, Seoul, Republic of Korea

The final, formatted version of the article will be published soon.

    Background: Sepsis, characterized by a dysregulated host response to infection, often leads to organ dysfunction, and vascular endothelial dysfunction plays a central role. The erythropoietin-producing hepatocellular carcinoma (Eph)A2 receptor is associated with increased vascular permeability; however, the developmental endothelial locus-1 (Del-1), has contrasting effects on endothelial function. Hence, we examined their potential as biomarkers of sepsis. Methods: In total, 117 participants, including 20 healthy controls, 21 patients with postoperative systemic inflammatory response syndrome (SIRS), and 76 patients with sepsis, were enrolled in this study. Sepsis severity was assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Sequential Organ Failure Assessment (SOFA) scores. Results: The Median plasma EphA2 levels increased progressively from healthy controls to SIRS and sepsis cases (154.29, 293.52, and 554.24 pg/mL; all p<0.05). The median plasma Del-1 levels were highest in healthy controls, lowest in SIRS, and intermediate level in sepsis (101.27, 16.88, and 36.9 pg/mL; all p<0.001). The levels of both biomarkers were higher in 28-day non-survivors than in survivors, in patients with sepsis (EphA2:898.09 vs. 475.88 pg/mL, p<0.001; Del-1:46.09 vs. 32.68 pg/mL, p=0.193); however, only EphA2 was statistically significant. The area under the curve for the EphA2 was 0.74 in the receiver operating characteristic curve analysis for predicting 28-day mortality, whereas APACHE II, SOFA, and Del-1 showed values of 0.762, 0.614, and 0.595, respectively. Kaplan-Meier analysis using these cutoffs revealed that survival was significantly higher in the group with both low EphA2 and Del-1 levels compared to the group with high levels of both markers (p < 0.001). Conclusion: Plasma EphA2 levels consistently increased with sepsis severity, suggesting its biomarker value for sepsis diagnosis and prognosis. In contrast, plasma Del-1 response was variable, indicating its limited prognostic utility.

    Keywords: EphA2, Del-1, Sepsis, biomarker, diagnosis, prognosis

    Received: 03 Oct 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 LEE, Shin, Kwak, Choi, Leem, Lee, Chung, KIM, Lee and Park. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Moo Suk Park, College of Medicine, Yonsei University, Seoul, Republic of Korea

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