Potential of circulating lncRNA CASC2 as a biomarker in reflecting the inflammatory cytokines, multi-organ dysfunction, disease severity, and mortality in sepsis patients

Background: Long noncoding RNA (lncRNA) cancer susceptibility candidate gene 2 (CASC2) inhibits inflammation and multi-organ dysfunction in various ways. The present study was intended to explore the potency of blood lncRNA CASC2 as a biomarker for sepsis management.

Methods: Totally, 184 sepsis patients and 30 healthy controls were enrolled. The reverse transcription-quantitative polymerase chain reaction was used to detect lncRNA CASC2 expression in peripheral blood mononuclear cell samples from the subjects. Mortality during 28 days was recorded in sepsis patients.

Results: LncRNA CASC2 was decreased in sepsis patients [median (interquartile range [IQR]): 0.473 (0.241-0.773)] by comparison to healthy controls [median (IQR): 1.019 (0.676-1.685)] (p < 0.001). In sepsis patients, lncRNA CASC2 was negatively correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II) (p = 0.001), Sequential Organ Failure Assessment (SOFA) (p < 0.001), SOFA-respiratory system (p = 0.010), SOFA-coagulation (p = 0.020), SOFA-liver (p = 0.019), and SOFA-renal (p = 0.010) scores, but was not related to SOFA-nervous (p = 0.466) and SOFA-cardio vascular system (p = 0.059) scores. Additionally, lncRNA CASC2 was negatively related to tumor necrosis factor-α (p = 0.024), interleukin (IL)-1β (p = 0.013), and IL-17A (p = 0.002), but was not linked to IL-6 (p = 0.112) or IL-10 (p = 0.074). Furthermore, lncRNA CASC2 was lower in sepsis deaths [median (IQR): 0.286 (0.166-0.475)] than in survivors [median (IQR): 0.534 (0.296-0.811)] (p < 0.001). Simultaneously, Kaplan-Meier (KM) curve analysis also observed that lncRNA CASC2 was inversely related to accumulating mortality in sepsis patients (p = 0.003). While lncRNA CASC2 could independently predict lower mortality risk.

Conclusion: Circulating lncRNA CASC2 inadequacy indicates the release of inflammatory cytokines, severe multi-organ injuries, and increased mortality in sepsis patients.