Comprehensive Transcriptome Profiling in Sepsis Induced by Pyogenic Liver Abscess

Sepsis is a critical condition characterized by a dysregulated immune response to infection, leading to widespread inflammation, tissue damage, organ failure, and often death. It is a leading cause of morbidity and mortality, particularly in intensive care units (ICUs), due to its complex pathophysiology involving immune dysregulation, coagulation abnormalities, and metabolic disturbances. Among the various infections that can precipitate sepsis, pyogenic liver abscess (PLA) is a significant cause, especially in developing countries where its incidence is rising. PLA, an infectious liver disease, can lead to sepsis, termed sepsis secondary to PLA (SLA). This study aimed to identify key genes and non-coding RNAs involved in the pathogenesis and treatment of SLA. We performed RNA sequencing on peripheral blood samples from healthy individuals, SLA patients, and SLA patients after seven days of therapy. Integrated bioinformatics analysis identified 4,549 differentially expressed (DE) mRNAs, 9,808 DE lncRNAs, 467 DE circRNAs, and 292 DE miRNAs between SLA patients and healthy controls. Additionally, 3,199 mRNAs, 6,018 lncRNAs, 161 circRNAs, and 132 miRNAs were differentially expressed between SLA patients before and after seven days of therapy. DE mRNAs in both comparisons were associated with immune responses; DE lncRNAs were linked to the B cell receptor signaling pathway and osteoclast differentiation; DE circRNAs were connected to Chagas disease and the B cell receptor signaling pathway; and DE miRNAs were implicated in the MAPK and estrogen signaling pathways. We constructed lncRNA/circRNA-miRNA-mRNA networks to explore regulatory relationships, validating 16 ceRNAs through RT-PCR. These findings provide new insights into SLA pathogenesis and treatment, potentially guiding the development of novel therapies.