RGS1 can serve as a long-term prognostic marker in gastric cancer by promoting the infiltration and polarization of macrophages

Abstract

Gastric cancer (GC) remains a prevalent and aggressive malignancy worldwide, characterized by significant morbidity and mortality. The regulator of G-protein signaling 1 (RGS1) plays an oncogenic role in various cancers, including GC, but its clinical relevance and mechanisms remain underexplored. In this pilot study, we investigated RGS1 expression in GC tissues and its potential as a prognostic marker, laying the groundwork for future research. Our analysis of patient data from the TCGA data and our cohort of 375 surgically resected GC patients revealed that RGS1 was upregulated in GC tissues and had prognostic significance (TCGA: adjusted HR:1.49, 95%CI: 1.02–2.18; GC cohort: adjusted HR: 1.38, 95%CI: 1.02–1.85). GO function and KEGG enrichment analyses suggest that RGS1 is involved in macrophage-mediated immune responses in GC. We observed a positive correlation between RGS1 expression and M2 macrophage infiltration. Furthermore, co-occurrence of elevated RGS1 expression and M2 macrophage infiltration predicts a worse prognosis (adjusted HR: 1.73, 95%CI: 1.24–2.42 in our cohort). In vitro, RGS1 upregulation and the presence of M2 macrophages enhanced malignant phenotypes of GC cells. Additionally, we confirmed that RGS1 promoted macrophage recruitment and M2 polarization via upregulation of CCL4 expression in vivo. In conclusion, this study suggests that RGS1 could serve as a promising prognostic marker for GC and a potential target for immunotherapy. However, further investigation with more advanced experimental models is needed to confirm these preliminary findings.