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

• Published in: Shock (Augusta, Ga.) Ga.), 2023-06, Vol.59 (6), p.855-863
• Main Authors: Ruan, Hang, Li, Yao-zhuo, Zhang, Qin, Wang, Bin-ran, Wu, Rongxue, Li, Shu-sheng, Ran, Xiao
• Format: Article
• Language: English
• Subjects: Clinical Science Aspects; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Sepsis - metabolism
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/SHK.0000000000002122

Objective: Sepsis is a complex disease characterized by an inflammatory response and tissue hypoxia. Hypoxia-inducible factor 1α (HIF-1α) expression level is regulated by hypoxia and inflammation. This study aimed to explore the correlation between HIF-1α 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-1α protein level in 54 nonseptic patients and 173 septic patients who were followed up for 28 days. Results: Bioinformatics analysis revealed that HIF-1α messenger RNA level was significantly different between septic and nonseptic patients ( P < 0.05). Consistent with the study hypothesis, higher HIF-1α 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-1α expression level combined with oxygen saturation to fraction of inspired oxygen (SpO 2 /FiO 2 ), white blood cell, and blood urea nitrogen. The HIF-1α 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-1α expression level and intensive care unit (ICU) mortality. Univariate and multivariate linear regression analyses indicated that septic patients with the elevated HIF-1α expression levels had shorter length of ICU stay versus those with the lower HIF-1α expression levels. Conclusion: Hypoxia-inducible factor 1α expression level can be used for diagnosing disease, assessing severity, and predicting length of ICU stay in septic patients.