Untargeted Metabolomic Profiling of the Correlation Between Prognosis Differences and PD-1 Expression in Sepsis: A Preliminary Study

Abstract

Objectives: The mortality rate of sepsis remains very high. Metabolomic techniques are playing increasingly important roles in diagnosis and treatment in critical care medicine. The purpose of our research was to use untargeted metabolomics to identify and analyze the common differential metabolites among patients with sepsis with differences in their 7-day prognosis and blood PD-1 expression and analyze their correlations with environmental factors. Methods: Plasma samples from 18 patients with sepsis were analyzed by untargeted LC-MS metabolomics. Based on the 7-day prognoses of the sepsis patients or their levels of PD-1 expression on the surface of CD4+ T cells in the blood, we divided the patients into two groups. We used a combination of multidimensional and monodimensional methods for statistical analysis. At the same time, the Spearman correlation analysis method was used to analyze the correlation between the differential metabolites and inflammatory factors. Results: In the positive and negative ionization modes, 16 and 8 differential metabolites were obtained between the 7-day death and survival groups, respectively; 5 and 8 differential metabolites were obtained between the high PD-1 and low PD-1 groups, respectively. We identified three common differential metabolites from the two groups, namely, PC (P-18:0/14:0), 2-ethyl-2-hydroxybutyric acid and glyceraldehyde. Then, we analyzed the correlations between environmental factors and the common differences in metabolites. Among the identified metabolites, 2-ethyl-2-hydroxybutyric acid was positively correlated with the levels of IL-2 and lactic acid (Lac) (P < 0.01 and P < 0.05, respectively). Conclusions: These three metabolites were identified as common differential metabolites between the 7-day prognosis groups and the PD-1 expression level groups of sepsis patients. They may be involved in regulating the expression of PD-1 on the surface of CD4+ T cells through the action of related environmental factors such as IL-2 or Lac, which in turn affects the 7-day prognosis of sepsis patients.

Keywords: PD-1; differential metabolites; prognosis; sepsis; untargeted metabolomics.