Plasma Vanin-1 as a Novel Biomarker of Sepsis for Trauma Patients: A Prospective Multicenter Cohort Study

Abstract

Introduction: Vanin-1 plays a pivotal role in oxidative stress and the inflammatory response. However, its relationship with traumatic sepsis remains unknown. The aim of our study was to evaluate whether plasma vanin-1 could be used for the early prediction of traumatic sepsis.

Methods: In this three-stage prospective cohort study, severe trauma patients admitted from January 2015 to October 2018 at two hospitals were enrolled. Plasma vanin-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The associations among variables and traumatic sepsis were identified by logistic regression models and the receiver operating characteristic (ROC) curve was analyzed to evaluate the diagnostic efficiency.

Results: A total of 426 trauma patients (22 in the discovery cohort, 283 in the internal test cohort, and 121 in the external validation cohort) and 16 healthy volunteers were recruited. The plasma vanin-1 of trauma patients was significantly higher than that of healthy volunteers (P < 0.05). Patients with sepsis had higher plasma vanin-1 than patients without sepsis in the discovery trauma cohort (P < 0.05). In the internal test cohort, plasma vanin-1 at day 1 after trauma was significantly associated with the incidence of sepsis (OR = 3.92, 95% CI 2.68-5.72, P = 1.62 × 10^-12). As a predictive biomarker, vanin-1 afforded a better area under the curve (AUC) (0.82, 95% CI 0.77-0.87) than C-reaction protein (CRP) (0.62, 95% CI 0.56-0.68, P < 0.0001), procalcitonin (PCT) (0.66, 95% CI 0.60-0.71, P < 0.0001), and Acute Physiology and Chronic Health Evaluation II (APACHE II) (0.71, 95% CI 0.65-0.76, P = 6.70 × 10^-3). The relevance was further validated in the external validation cohort (OR = 4.26, 95% CI 2.22-8.17, P = 1.28 × 10^-5), with an AUC of 0.83 (95% CI 0.75-0.89). Vanin-1 could also improve the diagnostic efficiency of APACHE II (AUC = 0.85).

Conclusions: Our study demonstrated that plasma vanin-1 increased among trauma patients and was independently associated with the risk of sepsis. Vanin-1 might be a potential biomarker for the early prediction of traumatic sepsis.

Trial registration: Clinicaltrials.gov Identifier, NCT01713205.

Keywords: Biomarker; Sepsis; Trauma; Vanin-1.

Fig. 1

Kinetics of plasma vanin-1 levels in trauma patients on admission and at days 3, 5, 7, and 14 during hospitalization from the discovery cohort. a Plasma vanin-1 of trauma patients is significantly higher than that of healthy volunteers (n = 22 trauma patients vs. 16 healthy controls). b Trauma patients with sepsis have higher plasma vanin-1 than patients without sepsis at the early stage after injury (n = 11 patients with sepsis vs. 11 patients without sepsis, P = 0.03 for day 1 and P = 0.04 for day 3). Data are expressed as the mean and 95% CI. Statistical analysis comprised Student’s t test

Fig. 2

Plasma vanin-1 in trauma patients with and without sepsis for the a internal test and b external validation cohorts. Patients who developed sepsis had significantly higher levels of plasma vanin-1 when compared with patients who did not develop sepsis at day 1 after trauma. All samples were collected on day 1 after injury. Black bars show the mean and 95% CI. Statistical analysis comprised Student’s t test

Fig. 3

Receiver operating curve (ROC) analysis of VNN1, CRP, PCT, and APACHE II for sepsis after trauma. Plasma vanin-1 afforded the best predictive value compared to other biomarkers and scores in the internal test cohort (a, n = 283) and external validation cohort (b, n = 121)