Abstract
Gastric cancer (GC) is a common malignant tumour and a leading cause of cancer-related deaths worldwide. Although the OAS gene family has been implicated in various tumour-related biological processes, its specific role in GC remains unclear. This study integrated bioinformatics analysis of public datasets with experimental validation using clinical GC specimens to investigate the function of the OAS gene family in GC. We found that OAS family members were significantly upregulated in GC and associated with poor patient prognosis. Furthermore, OAS expression levels correlated with genomic mutation profiles and showed positive associations with neutrophil and dendritic cell infiltration in the tumour microenvironment, but negative correlation with B cell infiltration. In vitro functional experiments demonstrated that knockdown of OAS3 or OASL inhibited GC cell proliferation and migration, while overexpression of OASL enhanced these malignant behaviors. RNA-seq analysis revealed upregulation of SFRP4 and JUN and downregulation of ACTA2. KEGG pathway analysis indicated significant enrichment in necroptosis, MAPK signaling, PI3K-Akt signaling, cAMP signaling, viral carcinogenesis, cancer pathways, neutrophil extracellular trap formation, and IL-17 signaling pathways. Additionally, OASL may regulate DNA damage response and metabolic reprogramming. Drug prediction and molecular docking identified chlorendic acid, idarubicin, PHA-848,125, and tosedostat as potential activators of the OAS family due to their strong binding affinity. Conversely, GW842166, NSC 23,766, and metolazone showed high binding affinity for OASL and may inhibit its expression. In summary, The OAS gene family, associated with poor prognosis in gastric cancer, promotes tumour progression and represents a promising therapeutic target.