Expressional and Prognostic Value of GPNMB in Gastric Cancer via Integrated Bioinformatics Analyses

Introduction Gastric Cancer (GC) is a major global health problem with high incidence and mortality, making it necessary to find new prognostic biomarkers. Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB) has been linked to tumor growth in several cancers, but its role as a prognostic marker in GC remains unclear. Methods To explore GPNMB’s expression, immune microenvironment association, and prognostic value in GC, this study integrated bioinformatics (TCGA, GEO, GEPIA) and Immunohistochemistry (IHC) on 73 paired GC/adjacent tissues, with semi-quantitative scoring and statistical analyses (chi-square, Mann-Whitney U, log-rank, multivariate Cox regression). Results GPNMB was significantly overexpressed in GC tissues vs. adjacent tissues (IHC: 57 ± 53 vs. 38 ± 39, p = 0.018; consistent with TCGA/GEO). High GPNMB correlated with abnormal immune/stromal scores (F = 6.55, Pr(>F) = 0.000249), increased immunosuppressive cell infiltration, decreased effector T cells, advanced M stage (distant metastasis rate: 24.2% vs. 5.0%, p = 0.017), shorter overall survival (log-rank p = 0.018), and was an independent prognostic factor (HR = 1.52, 95% CI:1.03–2.24, p = 0.035; multi-dataset HR:1.446–1.7, p < 0.05). Females showed a higher proportion of GPNMB (36.4% vs. 17.5% males), but this difference was not significant ( p = 0.068). Discussion Our study confirms GPNMB’s overexpression in gastric cancer via integrated bioinformatics and IHC, linking it to immune microenvironment dysregulation, distant metastasis, and poor prognosis-reinforcing its role as an independent prognostic biomarker and potential immunotherapy target, while noting limitations of small single-center IHC cohort, lack of experimental validation for relevant signaling pathway involvement, and reliance on algorithmic immune infiltration analyses. Conclusion GPNMB is overexpressed in GC, drives progression (especially metastasis), and shortens survival by regulating the immune microenvironment to exacerbate immune escape. It serves as an independent GC prognostic marker for risk stratification and a potential target for combined immunotherapy.