Tenascin-C, presepsin (sCD14-ST), and neutrophil-to-lymphocyte ratio as complementary circulating biomarkers for sepsis-associated organ dysfunction and 28-day all-cause mortality: a biomarker-enriched prognostic model
Circulating biomarkers and prognosis in sepsis
Keywords:
Tenascin-C, Presepsin (sCD14-ST), Sepsis-associated organ dysfunction, Biomarker-based risk stratification, 28-day mortality
Abstract
Background: Sepsis is characterized by dysregulated host responses with subsequent organ dysfunction. Conventional biomarkers (e.g., procalcitonin) incompletely reflect tissue injury and immune activation. We evaluated the clinical laboratory value of circulating Tenascin-C (TNC), presepsin (sCD14-ST), and the neutrophil-to-lymphocyte ratio (NLR) as complementary biomarkers of organ dysfunction severity and short-term prognosis in sepsis.
Methods: This retrospective observational study enrolled 103 adult ICU patients fulfilling Sepsis-3 criteria (June 2023–June 2025). Peripheral blood was collected within 12 h of ICU admission. Serum TNC was measured by ELISA; sCD14-ST was quantified by chemiluminescent enzyme immunoassay; NLR was calculated from routine blood counts. Associations with organ dysfunction were assessed using Spearman correlation with SOFA scores. Independent associations with 28-day all-cause mortality were examined using multivariable logistic regression. Predictive performance of a clinical baseline model (age, SOFA, PCT) versus a biomarker-enriched model (baseline + TNC, sCD14-ST, NLR) was evaluated by ROC analysis.
Results: TNC, sCD14-ST, and NLR were higher in septic shock than sepsis and were elevated in non-survivors versus survivors (all P < 0.05). TNC showed the strongest correlation with SOFA (r = 0.466, P < 0.001), followed by sCD14-ST (r = 0.352, P < 0.001) and NLR (r = 0.299, P = 0.002). In multivariable analysis, TNC, sCD14-ST, and NLR remained independently associated with 28-day all-cause mortality. The biomarker-enriched model improved discrimination compared with the baseline model (AUC 0.928 vs. 0.867), with higher sensitivity (84.4% vs. 71.9%).
Conclusions: Admission TNC, sCD14-ST, and NLR capture complementary biochemical dimensions of sepsis (tissue injury, innate immune activation, and immune imbalance) and improve risk stratification for organ dysfunction and 28-day all-cause mortality when added to routine clinical variables. These findings support a pragmatic, laboratory-based multimarker approach for early prognostic assessment in sepsis. Keywords: Tenascin-C; Presepsin (sCD14-ST); Sepsis-associated organ dysfunction; Biomarker-based risk stratification; 28-day all-cause mortality.
References
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15. Takahashi G, Hoshikawa K, Suzuki R, Sato K, Hoshi S, Yoshinao D, et al. Development of a newly immunoassay specific for mouse presepsin (sCD14-ST). Sci Rep-Uk 2022; 12(1): 21724.
16. Zhu Y, Li X, Guo P, Chen Y, Li J, Tao T. The accuracy assessment of presepsin (sCD14-ST) for mortality prediction in adult patients with sepsis and a head-to-head comparison to PCT: a meta-analysis. Ther Clin Risk Manag 2019; 15: 741-53.
17. Xu Z, Zhang J, Li Z, Wu H, Xu H, Guo Y, et al. Organ-targeted biomarkers of sepsis: A systematic review reveals the value of inflammation and lipid metabolic dysregulation. Pharmacol Res 2025; 219: 107917.
18. Gao Z, Wang X, Wang W, Kang Z, Chen X. Association between neutrophil to lymphocyte ratio and the mortality of patients with sepsis: an update systematic review and meta-analysis. Front Med-Lausanne 2025; 12: 1637365.
19. Huang Z, Ge H, Sun Y. Association between Neutrophil-to-Albumin Ratio and 28-Day All-Cause Mortality in Patients with Traumatic Brain Injury: A Retrospective Analysis of the MIMIC-IV Database. J Korean Neurosurg S 2025; 68(6): 736-48
2. Ashqar E, Alkaissi A, Ateeq O, Shawahna R. Factors predicting discharge outcomes of sepsis patients admitted to intensive care unit in a major tertiary care hospital: A retrospective study from Palestine. PLOS Global Public Health 2025; 5(12): e0005643.
3. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intens Care Med 2021; 47(11): 1181-247.
4. Chen L, Zhang X, Shi P. Recent advances in biomarkers for detection and diagnosis of sepsis and organ dysfunction: a comprehensive review. Eur J Med Res 2025; 30(1): 1081.
5. Marzeda AM, Midwood KS. Internal Affairs: Tenascin-C as a Clinically Relevant, Endogenous Driver of Innate Immunity. The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society 2018; 66(4): 289-304.
6. Piccinini AM, Midwood KS. DAMPening inflammation by modulating TLR signalling. Mediat Inflamm 2010; 2010: 672395.
7. Wu H, Yang M, Yan C, Liu M, Wang H, Zhang W. Tenascin C activates the toll‑like receptor 4/NF‑κB signaling pathway to promote the development of polycystic ovary syndrome. Mol Med Rep 2024; 29(6): 106.
8. Yuan W, Zhang W, Yang X, Zhou L, Hanghua Z, Xu K. Clinical significance and prognosis of serum tenascin-C in patients with sepsis. Bmc Anesthesiol 2018; 18(1): 170.
9. Chenevier-Gobeaux C, Borderie D, Weiss N, Mallet-Coste T, Claessens Y. Presepsin (sCD14-ST), an innate immune response marker in sepsis. Clinica Chimica Acta; International Journal of Clinical Chemistry 2015; 450: 97-103.
10. van Leeuwen LM, Fourie E, van den Brink G, Bekker V, van Houten MA. Diagnostic value of maternal, cord blood and neonatal biomarkers for early-onset sepsis: a systematic review and meta-analysis. Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases 2024; 30(7): 850-7.
11. Huang Z, Fu Z, Huang W, Huang K. Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: A meta-analysis. The American Journal of Emergency Medicine 2020; 38(3): 641-7.
12. Buonacera A, Stancanelli B, Colaci M, Malatino L. Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases. International Journal of Molecular Sciences 2022; 23(7): 3636.
13. Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama-J Am Med Assoc 2016; 315(8): 762-74.
14. Wang Y, Wen X, Su C, You Y, Jiang Z, Fan Q, et al. The role of tenascin-C in tumor microenvironments and its potential as a therapeutic target. Front Cell Dev Biol 2025; 13: 1554312.
15. Takahashi G, Hoshikawa K, Suzuki R, Sato K, Hoshi S, Yoshinao D, et al. Development of a newly immunoassay specific for mouse presepsin (sCD14-ST). Sci Rep-Uk 2022; 12(1): 21724.
16. Zhu Y, Li X, Guo P, Chen Y, Li J, Tao T. The accuracy assessment of presepsin (sCD14-ST) for mortality prediction in adult patients with sepsis and a head-to-head comparison to PCT: a meta-analysis. Ther Clin Risk Manag 2019; 15: 741-53.
17. Xu Z, Zhang J, Li Z, Wu H, Xu H, Guo Y, et al. Organ-targeted biomarkers of sepsis: A systematic review reveals the value of inflammation and lipid metabolic dysregulation. Pharmacol Res 2025; 219: 107917.
18. Gao Z, Wang X, Wang W, Kang Z, Chen X. Association between neutrophil to lymphocyte ratio and the mortality of patients with sepsis: an update systematic review and meta-analysis. Front Med-Lausanne 2025; 12: 1637365.
19. Huang Z, Ge H, Sun Y. Association between Neutrophil-to-Albumin Ratio and 28-Day All-Cause Mortality in Patients with Traumatic Brain Injury: A Retrospective Analysis of the MIMIC-IV Database. J Korean Neurosurg S 2025; 68(6): 736-48
Published
2026/02/23
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