Screening of Differentially Expressed Genes Based on the ACRG Molecular Subtypes of Gastric Cancer and the Significance and Mechanism of 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 () gene were bioinformatically analyzed and experimentally verified. The role of 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 was poor ( < 0.05). The gene in GC samples was associated with the expression of immune pathways and immune checkpoint genes. After modifying 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 was a molecular feature of MSS/EMT type gastric cancer. Further study found that was closely related to tumor immune infiltration and invasion and may be a new therapeutic target gene for gastric cancer.