191P - Predictive value of CXCR6 expression in gastric cancer survival and immune modulation

Background

Gastric cancer (GC) is a major global health concern, with prognosis influenced by tumor stage and its microenvironment, especially immune cell presence. This research investigates the relation between CD8 T cell expression, emphasizing CXCR6, and GC survival outcomes.

Methods

Using TCGA-STAD RNA-seq data, we studied a cohort of 280 Stage 2 and 3 GC patients. CD8 T cell expression was examined through X Cell Analysis, followed by Cutoff Determination via R package Maxstat. Post categorization into CD8L and CD8H groups, Differential Gene Expression Analysis identified 495 upregulated and 102 downregulated genes. Weighted Gene Co-expression Network Analysis highlighted CXCR6's importance. Correlations between CXCR6, immune cell infiltration, and survival patterns were explored. Verification came from GES 62254 data and Immunohistochemical Staining of a sample from Dong-A University Hospital.

Results

The findings reveal that heightened CXCR6 expression is significantly associated with improved survival outcomes in both recurrence-free survival (RFS) and overall survival (OS) using TCGA-STAD data. Importantly, the validation using GES 62254 data consistently supports these results. Moreover, the study delves into the tumor microenvironment using TCGA-STAD RNA-seq data, showcasing a positive link between CXCR6 expression and immune cell presence, particularly CD8 T cells, T cell gamma delta cells, NK cells, and activated DCs. This suggests a potential reinforcement of anti-tumor responses. The research further uncovers correlations between CXCR6 expression and markers of CD8 T cell activation, as well as the activation of DCs.Importantly, a clinical investigation involving GC patients treated at Dong-A University Hospital supports the statistical significance of increased CXCR6 expression in relation to enhanced survival rates.

Conclusions

Our research showcases the relationship between enhanced CXCR6 expression and improved GC patient survival. It presents CXCR6 as a potential prognostic biomarker, underscoring its role in the tumor immune milieu. The focus on CD8 T cells and immune pathways suggests promising therapeutic directions, marking a step toward precision-based GC interventions.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

National foundation of Korea grant.

Disclosure

The author has declared no conflicts of interest.