IDENTIFICATION AND CLINICAL VALIDATION OF HYPOXIA-INDUCIBLE FACTOR 1a PROTEIN AS THE POTENTIAL BIOMARKER IN PATIENTS WITH SEPSIS

Objective: Sepsis is a complex disease characterized by an inflammatory response and tissue hypoxia. Hypoxia-inducible factor 1a (HIF-1a) expression level is regulated by hypoxia and inflammation. This study aimed to explore the correlation between HIF-1a expression level and sepsis by bioinformatics analysis and clinical investigation. Methods: Bioinformatics tools were used to identify differentially expressed genes between sepsis and nonsepsis groups using the Gene Expression Omnibus data set. A clinical investigation was carried out to validate HIF-1a protein level in 54 nonseptic patients and 173 septic patients who were followed up for 28 days. Results: Bioinformatics analysis revealed that HIF-1a messenger RNA level was significantly different between septic and nonseptic patients (P < 0.05). Consistent with the study hypothesis, higher HIF-1a levels in plasma were found in septic patients compared with those in nonseptic patients. The diagnostic accuracy for sepsis, as quantified by the area under the curve, was 0.926 (0.885-0.968) for HIF-1a expression level combined with oxygen saturation to fraction of inspired oxygen (SpO(2)/FiO(2)), white blood cell, and blood urea nitrogen. The HIF-1a expression level was also significantly correlated with the severity of the disease. The results of the restricted cubic splines model indicated a U-shaped relationship between HIF-1a expression level and intensive care unit (ICU) mortality. Univariate and multivariate linear regression analyses indicated that septic patients with the elevated HIF-1a expression levels had shorter length of ICU stay versus those with the lower HIF-1a expression levels. Conclusion: Hypoxia-inducible factor 1a expression level can be used for diagnosing disease, assessing severity, and predicting length of ICU stay in septic patients.