TY - JOUR
T1 - Integrative bioinformatics analysis reveals CGAS as a ferroptosis-related signature gene in sepsis and screens the potential natural inhibitors of CGAS
AU - Chen, Jiaxi
AU - Feng, Mingmei
AU - Zhang, Tianyao
AU - Zhong, Mengling
AU - Wang, Yupeng
AU - Zhang, Qi
AU - Sun, Yang
N1 - Publisher Copyright:
© 2025 Elsevier B.V.
PY - 2025/3
Y1 - 2025/3
N2 - Sepsis is a fatal organ dysfunction characterized by the simultaneous hyperinflammation and immunosuppression. Nowadays, the early precision intervention of sepsis is challenging. Ferroptosis is involved in the development of sepsis. The current study aimed to find out the signature genes of sepsis with network topology analysis and machine learning, and further provide the potential natural compounds for sepsis with virtual screening and in vitro validation. In this study, five genes namely CGAS, DPP4, MAPK14, PPARG and TXN were identified as ferroptosis-related signature genes for sepsis by network topological analysis, machine learning algorithms, and external datasets verification. The results of immune infiltration analysis confirmed these genes were significantly associated with the infiltration abundance of some immune cells including neutrophil, macrophage, plasmacytoid dendritic cell and activated dendritic cell. Moreover, coniferin, 5-O-caffeoylshikimic acid, and psoralenoside were initially identified as the natural inhibitors of CGAS by virtual screening. However, further in vitro study on macrophages revealed coniferin and psoralenoside had better inhibitory activities on CGAS. In summary, the present study pointed out the importance of CGAS in sepsis, and discovered novel natural inhibitors of CGAS.
AB - Sepsis is a fatal organ dysfunction characterized by the simultaneous hyperinflammation and immunosuppression. Nowadays, the early precision intervention of sepsis is challenging. Ferroptosis is involved in the development of sepsis. The current study aimed to find out the signature genes of sepsis with network topology analysis and machine learning, and further provide the potential natural compounds for sepsis with virtual screening and in vitro validation. In this study, five genes namely CGAS, DPP4, MAPK14, PPARG and TXN were identified as ferroptosis-related signature genes for sepsis by network topological analysis, machine learning algorithms, and external datasets verification. The results of immune infiltration analysis confirmed these genes were significantly associated with the infiltration abundance of some immune cells including neutrophil, macrophage, plasmacytoid dendritic cell and activated dendritic cell. Moreover, coniferin, 5-O-caffeoylshikimic acid, and psoralenoside were initially identified as the natural inhibitors of CGAS by virtual screening. However, further in vitro study on macrophages revealed coniferin and psoralenoside had better inhibitory activities on CGAS. In summary, the present study pointed out the importance of CGAS in sepsis, and discovered novel natural inhibitors of CGAS.
KW - CGAS
KW - Ferroptosis
KW - Immune infiltration
KW - Machine learning
KW - Sepsis
KW - Virtual screening
UR - http://www.scopus.com/inward/record.url?scp=85215360514&partnerID=8YFLogxK
U2 - 10.1016/j.ijbiomac.2025.139778
DO - 10.1016/j.ijbiomac.2025.139778
M3 - 文章
AN - SCOPUS:85215360514
SN - 0141-8130
VL - 297
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
M1 - 139778
ER -