Bioinformatic identification and experiment validation revealed ACTG1 is a promising prognostic signature and therapeutic target for sepsis.

In the Intensive Care Unit (ICU), sepsis is a prevalent clinical syndrome that is the final pathway to death from most infections. Peripheral blood gene expression profiling is becoming more and more accepted as a potential diagnostic or prognostic tool. This work aimed to recognize genes related to sepsis, providing potential translational therapeutic targets. RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 20 healthy controls and 51 sepsis patients. Weighted gene co-expression network analysis (WGCNA) was employed to pick out sepsis-related and immunocyte-related gene modules. Genes in the yellow module that are primarily involved in excessive inflammation and immune suppression. The STRING (https://string-db.org/) and CytoScape (https://cytoscape.org/) were combined to identify Actin Gamma 1(ACTG1) and Ras GTPase-activating-like protein IQGAP1(IQGAP1) as hub genes with highest connective degree, and prognostic predication value of ACTG1 was confirmed. Both univariate and multivariate logistic regression analyses were carried out. ACTG1 mRNA expression was increased in animal and in cell-related sepsis models. siRNA revealed decreasing ACTG1 can reduce the in vitro sepsis model apoptosis. We have authenticated ACTG1 as a reliable signature of a poor outcome of sepsis and promising therapeutic targets for sepsis.