Screening of Differentially Expressed Genes Based on the ACRG Molecular Subtypes of Gastric Cancer and the Significance and Mechanism of AGTR1 Gene Expression.

BACKGROUND: The Asian Cancer Research Group (ACRG) classification is a molecular classification established based on the tissues of gastric cancer (GC) patients in Asia. Patients with different ACRG subtypes differ significantly with regard to treatment response and prognosis, which indicates that the ACRG molecular classification is more valuable than the traditional pathological classification. However, the specific differentially expressed genes (DEGs) and the value of the ACRG molecular subtypes of GC have not been studied in depth.

METHODS: Through the analysis of the GEO database, the DEGs in GC tissues of different ACRG molecular subtypes were investigated. The expression and mechanism of the screened angiotensin II receptor type 1 ( AGTR1 ) gene were bioinformatically analyzed and experimentally verified. The role of AGTR1 in GC cells was mainly investigated using CCK-8, wound-healing, transwell invasion assays, qRT-PCR, and Western blotting.

RESULTS: The bioinformatics results showed the presence of multiple DEGs in GC tissues with different ACRG molecular subtypes. Certain DEGs in GC tissues of different ACRG molecular subtypes have prognostic significance. AGTR1 levels in tumor tissues were significantly higher than in paired paracancerous tissues. The prognosis of GC patients with high expression of AGTR1 was poor ( p < 0.05). The AGTR1 gene in GC samples was associated with the expression of immune pathways and immune checkpoint genes. After modifying AGTR1 expression in cell lines, cells' proliferation, invasion, and migration abilities and the expression of related genes changed.

CONCLUSIONS: There were significant DEGs in GC tissues with different ACGR molecular types, among which the increased expression of AGTR1 was a molecular feature of MSS/EMT type gastric cancer. Further study found that AGTR1 was closely related to tumor immune infiltration and invasion and may be a new therapeutic target gene for gastric cancer.