Bioinformatics analysis identifies biomarkers associated with poor prognosis in diffuse-type gastric cancer

Gastric cancer (GC) is one of the most common malignancies of the digestive system. In diffuse-type GC, differentiation is relatively poor, and the probability of distant metastasis and lymph node metastasis is high, resulting in poor clinical prognosis. The purpose of this study was to identify specific genes that can predict the prognosis of different types of GC. Differentially expressed genes (DEGs) were screened in the GSE62254 dataset obtained from the Gene Expression Omnibus using the ‘limma’ and ‘survival’ R packages. A total of 355 survival-related DEGs were selected according to specific screening criteria, of which 293 were associated with diffuse-type GC and 62 with intestinal-type GC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for functional annotation and pathway enrichment analysis of DEGs. Using protein-protein interaction networks and Cytoscape software, three hub genes were identified in diffuse-type GC-associated DEGs, including angiotensinogen (AGT), C-X-C motif chemokine ligand 12 (CXCL12) and adrenoceptor β2 (ADRB2). Immunohistochemical staining and reverse transcription-quantitative PCR revealed that the expression levels of the three genes in diffuse-type GC samples were upregulated compared with in intestinal-type GC samples. Kaplan Meier analysis indicated that a higher expression levels of these three hub genes were associated with a poorer prognosis of diffuse-type GC. In summary, the present findings suggested that AGT, CXCL12 and ADRB2 might contribute to the progression of diffuse-type GC, and could serve as potential biomarkers or therapeutic targets for this disease.