Abstract
BACKGROUND: Gastric cancer (GC) is a molecularly heterogeneous disease with diverse clinical outcomes. Traditional classifications lack predictive accuracy, necessitating alternative molecular subtyping approaches for effective prognosis prediction. The Asian Cancer Research Group (ACRG) molecular subtypes, combined with immune-associated PD-L1 expression, offer a promising framework to predict patient outcomes and potentially guide treatment strategies in GC. METHODS: This study retrospectively analyzed 1007 primary GC patients who underwent surgical resection between January 2017 and June 2019 at the Fourth Hospital of Hebei Medical University. Comprehensive immunohistochemical and fluorescent PCR-capillary electrophoresis analyses were conducted to determine ACRG molecular subtypes (microsatellite instability [MSI], microsatellite stability with epithelial-mesenchymal transition [MSS/EMT], MSS/TP53(+), and MSS/TP53(-)) and PD-L1 expression. We assessed the relationship between these classifications and various clinicopathological parameters, including survival outcomes, using Cox regression and Kaplan-Meier analysis. RESULTS: The ACRG subtypes showed significant associations with clinicopathological features, including tumor invasion depth, Lauren classification, and HER2 status. The MSI subtype (6.7% of cases) was associated with higher PD-L1 positivity and a favorable prognosis, whereas the EMT subtype had the lowest 5-year survival rate (34.55%) and was predominantly linked to diffuse-type histology. PD-L1 positivity correlated with worse survival outcomes, with independent predictive value alongside ACRG subtypes (HR for PD-L1 = 1.759, p = 0.001; HR for ACRG = 5.144, p < 0.001). CONCLUSION: The combination of ACRG molecular subtyping and PD-L1 expression serves as an effective predictor of GC prognosis, facilitating tailored clinical decision-making. The ACRG-PD-L1 classification system offers a practical, cost-effective approach for routine clinical application, providing critical insight into GC heterogeneity. Further multicenter studies are needed to validate these findings and explore the impact of ACRG subtypes on therapy responses, particularly in immunotherapy settings.