AUTHOR=Wang Yuli , Fang Yuan , Zhao Fanchen , Gu Jiefei , Lv Xiang , Xu Rongzhong , Zhang Bo , Fang Zhihong , Li Yan 

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

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.810292

DOI=10.3389/fgene.2022.810292

ISSN=1664-8021

ABSTRACT=<p>Gastric cancer (GC) is a common malignant tumor of the digestive system. Recent studies revealed that high gamma-glutamyl-transferase 5 (<italic>GGT5</italic>) 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 <italic>GGT5</italic> and its correlation with immune cell infiltration in gastric cancer. First, we compared the differential expression of <italic>GGT5</italic> 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 <italic>GGT5</italic> and clinical characteristics. We also investigated the correlation of <italic>GGT5</italic> 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 <italic>GGT5</italic> was upregulated in gastric cancer tissues compared to normal tissues. High <italic>GGT5</italic> expression was significantly associated with T stage, histological type, and histologic grade (<italic>p</italic> &lt; 0.05). Moreover, gastric cancer patients with high <italic>GGT5</italic> expression showed worse 10-years overall survival (<italic>p</italic> = 0.008) and progression-free intervals (<italic>p</italic> = 0.006) than those with low <italic>GGT5</italic> expression. Multivariate analysis suggested that high expression of <italic>GGT5</italic> 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. <italic>GGT5</italic> 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 <italic>GGT5</italic> was positively co-expressed with immune-related genes and immune checkpoint genes. Functional analysis revealed that differentially expressed genes relative to <italic>GGT5</italic> were mainly involved in the biological processes of immune and inflammatory responses. In conclusion, <italic>GGT5</italic> 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.</p>