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Gastric cancer (GC) is a common malignant tumor of the digestive system. Recent studies revealed that high gamma-glutamyl-transferase 5 ( GGT5 ) expression was associated with a poor prognosis of gastric cancer patients. In the present study, we aimed to confirm the expression and prognostic value of  GGT5  and its correlation with immune cell infiltration in gastric cancer. First, we compared the differential expression of  GGT5  between gastric cancer tissues and normal gastric mucosa in the cancer genome atlas (TCGA) and GEO NCBI databases using the most widely available data. Then, the Kaplan-Meier method, Cox regression, and univariate logistic regression were applied to explore the relationships between  GGT5  and clinical characteristics. We also investigated the correlation of  GGT5  with immune cell infiltration, immune-related genes, and immune checkpoint genes. Finally, we estimated enrichment of gene ontologies categories and relevant signaling pathways using GO annotations, KEGG, and GSEA pathway data. The results showed that  GGT5  was upregulated in gastric cancer tissues compared to normal tissues. High  GGT5  expression was significantly associated with T stage, histological type, and histologic grade ( p  &amp;lt; 0.05). Moreover, gastric cancer patients with high  GGT5  expression showed worse 10-years overall survival ( p  = 0.008) and progression-free intervals ( p  = 0.006) than those with low  GGT5  expression. Multivariate analysis suggested that high expression of  GGT5  was an independent risk factor related to the worse overall survival of gastric cancer patients. A nomogram model for predicting the overall survival of GC was constructed and computationally validated.  GGT5  expression was positively correlated with the infiltration of natural killer cells, macrophages, and dendritic cells but negatively correlated with Th17 infiltration. Additionally, we found that  GGT5  was positively co-expressed with immune-related genes and immune checkpoint genes. Functional analysis revealed that differentially expressed genes relative to  GGT5  were mainly involved in the biological processes of immune and inflammatory responses. In conclusion,  GGT5  may serve as a promising prognostic biomarker and a potential immunological therapeutic target for GC, since it is associated with immune cell infiltration in the tumor microenvironment.

Identification of GGT5 as a Novel Prognostic Biomarker for Gastric Cancer and its Correlation With Immune Cell Infiltration