A prediction model using ferroptosis-related genes strongly predicted severe pneumonia prognosis (AUC 0.92), and PGD expression was significantly higher in sepsis than in CAP (p=0.008).
Observational
Do ferroptosis-related genes predict disease progression and prognosis in patients with severe community-acquired pneumonia?
Ferroptosis is activated in severe pneumonia, and ferroptosis-related genes like PGD may serve as prognostic biomarkers for disease progression.
Effect estimate: AUC 0.92
p-value: p=0.008
Abstract Rationale Community-acquired pneumonia (CAP) is an important cause of mortality worldwide and the mortality rate increases significantly when the disease progresses to severe CAP (SCAP), which remains one of the most devastating conditions in intensive care. Nevertheless, there remains a significant deficiency of biomarkers for the rapid identification of disease progression and prognosis and the availability of safe and effective therapeutic agents for SCAP. This study aimed to verify whether ferroptosis was activated in severe pneumonia and establish a prognostic model for severe respiratory infections. Methods Single-cell sequencing data of peripheral blood mononuclear cells (PBMC) from severe CAP and healthy controls were analyzed, and the ferroptosis score between the two groups were compared. The ferroptosis score of sepsis, CAP and control through bulk RNA-sequencing of PBMC were compared for further verification, and the key genes related to ferroptosis were screened through LASSO regression to construct a disease progression and prognosis prediction model for severe CAP. The expression of prognostic gene signature was measured by quantitative real time polymerase chain reaction (qRT-PCR). Results The degree of ferroptosis in patients with severe pneumonia was significantly higher than that in healthy controls. Single-cell RNA-sequencing has revealed that monocytes and dendritic cells were the main source for ferroptosis activation in severe pneumonia, among which dendritic cells, pro-inflammatory monocyte subsets and HLA-DR high monocyte subsets play the primary roles. The proportion of pro-inflammatory monocyte subsets in patients with SCAP was also significantly increased. In addition, ferroptosis is also significantly associated with cytokine storms, including interleukin-1, interleukin-6 and interleukin-8. Bulk RNA-sequencing indicated that ferroptosis scores were correlated with the severity of acute respiratory tract infections, and the scores of sepsis patients were significantly higher than those of CAP and the control group. The study developed a prediction model for severe pneumonia prognosis using ferroptosis-related genes. It demonstrated strong performance, achieving an AUC of 0.92 in the test set and 0.86 in the external cohort. The expression of PGD in sepsis patients was significantly higher than that in CAP patients (p=0.008). Conclusions This study confirmed that ferroptosis was significantly activated in patients with severe pneumonia, and ferroptosis-related genes can serve as predictive markers for disease progression and prognosis of severe pneumonia, which awaits further verification in prospective cohort studies. This abstract is funded by: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences
Wang et al. (Fri,) conducted a observational in Severe community-acquired pneumonia (SCAP). Ferroptosis-related gene signature (PGD) vs. Healthy controls and non-severe CAP was evaluated on Disease progression and prognosis prediction model performance (AUC) (AUC 0.92, p=0.008). A prediction model using ferroptosis-related genes strongly predicted severe pneumonia prognosis (AUC 0.92), and PGD expression was significantly higher in sepsis than in CAP (p=0.008).