Abstract 234P
Background
Gastric cancer is one of the most common malignancies worldwide and it is the third leading cause of cancer-related death in China. In recent years, the role of microbes in cancer has been highlighted. Helicobacter pylori infection is an independent pathogenic factor of gastric cancer. However, a number of studies have confirmed that the abundance of Helicobacter pylori decreased in gastric cancer tissues, and the influence mechanism of other microorganisms on the development and metastasis of gastric cancer remains unclear.
Methods
Utilizing non-targeted metabolomics, mass spectrometry detection, NAD metabolism analysis, Western Blot, cell experiments, and animal models to elucidate the molecular mechanisms underlying the promotion of gastric cancer metastasis by Acinetobacter baumannii.
Results
In this study, we found that Acinetobacter abundance was significantly increased in gastric cancer tissues. And it was found that the abundance of Acinetobacter was significantly correlated with the stage of gastric cancer. Experimental validation through Fluorescence In Situ Hybridization (FISH) confirmed the colonization of Acinetobacter baumannii in tumor tissues of gastric cancer patients. Acinetobacter baumannii was found to promote the NAD metabolism of cells by increasing the content of nicotinamide (NA) in the co-culture system, leading to an increase in 1-MNA levels. We demonstrated that Acinetobacter baumannii can promote gastric cancer metastasis by activating the NF-kB pathway of gastric cancer cells through metabolites in vivo and in vitro. Additionally, in the mouse model, we discovered that Acinetobacter baumannii can also promote the formation of neutrophil extracellular traps (NETs), thereby inducing epithelial-to-mesenchymal transition (EMT) and promoting the metastasis of gastric cancer.
Conclusions
The research elucidates Acinetobacter baumannii can promote the NAD metabolism of gastric cancer cells through the synthesis of NA, thus promoting the metastasis of gastric cancer. Also, this study provides a theoretical basis for the development of novel therapeutic approaches in the comprehensive management of gastric cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Natural Science Foundation of China.
Disclosure
All authors have declared no conflicts of interest.