B7-H3 and CD39 Co-Localization in Gastric Cancer: A Potential Prognostic Biomarker and Potential Dual-Target for Immunotherapy.

Abstract

IntroductionGastric cancer (GC) is a highly heterogeneous malignancy, necessitating novel therapeutic targets. B7-H3 and CD39, as immune checkpoints, are potential modulators of the tumor microenvironment and may influence the efficacy of immunotherapies.MethodsB7-H3, CD39, and CD8 expression was assessed via immunohistochemistry (IHC) in 268 GC tissues and 80 gastric precancerous lesions. The correlation between B7-H3 and CD39 expression was analyzed using Spearman's correlation. Multiplex immunohistochemistry (m-IHC) was employed to determine the co-localization of B7-H3 and CD39 in GC tissues. Kaplan-Meier survival analysis and Cox regression models were utilized to evaluate clinical outcomes in different patient subgroups.ResultsBoth B7-H3 and CD39 expression showed a stepwise increase during gastric carcinogenesis including chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN) to GC, with significantly higher expression levels in GC tissues compared to all precancerous lesions (P < .05). A significant positive correlation was observed between B7-H3 and CD39 expression (r = 0.2398, P < .001). Co-localization of B7-H3 and CD39 was detected within tumor nests and peritumoral regions and was significantly correlated with tumor volume (P = .017), tumor stage (P = .001), tumor depth (P = .002), lymph node metastasis (P = .005), lymph node involvement (P = .004) and distant metastasis (P = .028). Kaplan-Meier analysis revealed that patients with co-localized B7-H3 and CD39 expression exhibited significantly poorer prognosis (P = .0055). Cox regression analysis confirmed that this co-localization was a significant predictor of survival (P = .007) and an independent prognostic factor in multivariate analysis (P = .027).ConclusionThe co-localized expression of B7-H3 and CD39 in GC patients is strongly associated with poor prognosis. This dual-target expression pattern provides novel insights and a theoretical foundation for the development of dual-target immune checkpoint inhibitors as potential therapeutic strategies.