Differential Transcriptomic Profiling Between Patients With Sepsis-Induced Ards And Sepsis Without Ards 

Abstract

Introduction: Acute Respiratory Distress Syndrome (ARDS) develops in the lungs as a response to potent inflammatory triggers, and sepsis represents one of the most common causes of ARDS. It is a highly lethal syndrome with no effective therapies, and little is known about the pathways that trigger it. In this project we combine publicly available sepsis and ARDS patient datasets to identify early transcriptomic changes that may be targeted therapeutically in the future. Hypothesis: Proinflammatory, neutrophil-centric pathways are central to the pathogenesis of ARDS in septic patients.Methods: The GEO dataset repository was searched and available human transcriptomic data from patients with Sepsis and Sepsis+ARDS were combined and analyzed. Genes, gene sets and significant pathways that were differentially expressed or activated at a statistically significant level between the two groups were identified.Results: No independent genes were identified to be differentially expressed across the three studies. There were 6 gene sets that were up- or down-regulated across all studies (four and two respectively), and the Sphingosine-1-Phophate (S1P) pathway was the only pathway seen to become activated in septic patients with ARDS compared to those with sepsis alone. Conclusions: Limited consistent gene and gene set transcription hinders our ability to identify viable biomarkers or therapeutic targets in ARDS in the setting of sepsis, but S1P pathway intermediaries may be viable candidates.