Evaluating the potency of blood long noncoding RNA PVT1 as candidate biomarker reflecting inflammation, multiple organ dysfunction, and mortality risk in sepsis patients

Abstract

Objective: Long noncoding RNA plasmacytoma variant translocation 1 (lnc-PVT1) promotes septic inflammation and organ injuries via multiple ways, while its clinical engagement in sepsis management is indistinct. This study aimed to investigate its relationship with inflammation, multiple organ dysfunction, and mortality risk in sepsis patients.

Methods: Sepsis patients and age-/gender-matched healthy controls were enrolled; their lnc-PVT1 expression in plasma were detected by RT-qPCR. For sepsis patients only, the inflammatory cytokine levels (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-17A) in plasma were detected by ELISA. According to the survival data during 28-day follow-up, sepsis patients were divided into sepsis survivors and sepsis deaths.

Results: Lnc-PVT1 expression was increased in sepsis patients (N = 157) compared with healthy controls (N = 80) (p < 0.001). In sepsis patients, lnc-PVT1 was linked with higher acute physiology and chronic health evaluation II (APACHEII) score (p = 0.001), total sequential organ failure assessment (SOFA) score, and its most subitems (SOFA-respiratory system, SOFA-coagulation, SOFA-liver, SOFA-cardiovascular system, and SOFA-renal system scores) (all p < 0.01), but not SOFA-nervous system score (p = 0.091); it did not relate to primary infection sites either (p = 0.204). Furthermore, lnc-PVT1 correlated with increased C-reactive protein, TNF-α, IL-1β, and IL-17 in sepsis patients (all p < 0.01). Additionally, lnc-PVT1 expression was higher in sepsis deaths than that in sepsis survivors (p < 0.001), following receiver-operating characteristic curve disclosed that lnc-PVT1 predicted 28-day septic mortality risk (area under the curve: 0.789, 95% confidence interval: 0.702-0.875).

Conclusion: Circulating lnc-PVT1 exhibits the potential as a biomarker in sepsis patients to inform inflammation, multiple organ dysfunction, and mortality risk.

Keywords: inflammation; long noncoding RNA PVT1; mortality risk; multiple organ dysfunction; sepsis.