Deciphering the Role of CD14 in Helicobacter Pylori-associated Gastritis and Gastric Cancer: Combing Bioinformatics Analysis and Experiments.

Abstract

Background: Gastric cancer (GC) is the third leading cause of cancer-related death and is associated with high mortality and morbidity. Helicobacter pylori (HP) infection is the most important cause of GC. We aimed to identify the core genes of HP caused GC and further elucidate the underlying mechanisms. Methods: GC and HP associated gastritis (HPAG) gene expression data were sourced from Gene Expression Omnibus. Key genes affecting GC prognosis were identified using Cytoscape software. Patient groups were formed based on key gene expression, and the immune analyses were performed with R. MNU, derived from nitrite by HP, was given to GC mice (240ppm) for histology and fluorescence assays. For in vitro experiments, cells received MNU (20 μM) stimulation for 24 hours. Results: CD14 was the only key gene identified. A total of 412 GC patients were divided into CD14-high and CD14-low groups. The two groups showed significant differences in immune cell populations and immune checkpoints. In particular, there was a notable increase in M2 macrophages in GC patients with high CD14 expression (P <0.001). GC Patients with high CD14 expression exhibited a more pronounced immune response than those with low CD14 expression, and elevated CD14 expression positively correlated with the efficacy of CTLA4 therapy (P <0.05). These results indicated that CD14 expression was strongly correlated with the GC immune response. A noticeable increase in CD14 levels was observed in MNU-induced GC animals, cell models, and GC patients. In addition, the number of M2 macrophages was increased in MNU-induced GC mice. Conclusion: Reducing CD14 expression may increase the survival rate of GC patients through the modulation of immune responses. The complex mechanism of CD14's influence on prognosis deserves further investigation.