Exploring the role of OSMR in gastric cancer: from oncogenic functions to relevant immune features

Abstract

The Oncostatin M receptor (OSMR) has been demonstrated to play a key regulatory role in multiple cancer types; however, the functional role of OSMR in gastric cancer (GC) remains poorly understood. This study aimed to investigate OSMR expression in GC, its association with clinical and histopathological features, its prognostic significance, and its potential involvement in the tumor immunological microenvironment. OSMR expression levels were assessed through immunohistochemistry and western blotting. Our findings revealed that OSMR was significantly upregulated in most tumor types. Experimental and database analyses demonstrated that OSMR expression was elevated in GC and correlated with poor prognosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) indicated that high OSMR expression may activate the JAK-STAT, PI3K-AKT, and Focal Adhesion signaling pathways. Moreover, an OSMR-derived genomic model demonstrated high accuracy in predicting clinical outcomes among gastric cancer patients. A nomogram incorporating age and the OSMR-derived risk score was employed to more precisely estimate an individual's probability of survival. Additionally, elevated OSMR levels were correlated with increased immune cell infiltration and diminished response to immunotherapy. Finally, silencing OSMR significantly inhibited tumor cell proliferation, invasion, and migration, while markedly reducing the phosphorylation of JAK3 and STAT3, as well as the expression of HIF-1α, VEGFA, and PD-L1. In summary, our findings indicate that OSMR plays a pivotal role in regulating tumor progression and the immune microenvironment in gastric cancer through the JAK/STAT3/HIF-1α signaling pathway.

Keywords: Gastric cancer; Immune microenvironment; OSMR; Prognosis.