Identification of the Expression of TIE1 and Its Mediated Immunosuppression in Gastric Cancer

Abstract

Background: Recently, various evidence has confirmed that Tyrosine Kinase with Immunoglobulin-like and EGF-like domains 1 (TIE1) promotes tumor growth in many cancers. However, the precise mechanism underlying TIE1's involvement in Gastric Cancer (GC) remains elusive. This research aimed to investigate the biological function of TIE1 in regulating GC progression. Methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), GEPIA2.0, Sangerbox3.0 and TIMER databases were used to analyze the TIE1 expression. Immunohistochemistry (IHC) was used to demonstrate the expression of TIE1. TCGA, GEPIA2.0 and Kaplan-Meier were utilized for survival analysis and to explore the association of TIE1 with clinicopathological features. Protein-Protein Interaction (PPI) networks were constructed using Cytoscape. The potential molecular mechanism of TIE1 was investigated by Gene Ontology (GO), Kyoto Encyclopedia of Gene Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). We studied the relationships between TIE1 and mutations, immune checkpoints (ICs), tumor mutational burden (TMB), as well as microsatellite instability (MSI) to explore the underlying mechanism of immunity in GC. Results: Compared with normal tissue, TIE1 was significantly overexpressed in GC tissues (p = 0.0072) and was associated with poor survival (P < 0.05). According to GO and KEGG enrichment analyses, TIE1 was enriched in signal pathways related to the occurrence, invasion, and migration of malignant tumors (i.e., PI3K-Akt signaling pathway, Calcium signaling pathway, etc.). Immune infiltration analysis suggested that TIE1 is positively correlated with macrophages M2 and negatively correlated with Mast cells, naive B cells and Follicular helper T cells (TFH), which may be a contributing factor to tumor progression. Furthermore, the research on the tumor microenvironment (TME) and tumor purity also proved that TIE1 may be an oncogene. Mutation analysis showed that the high expression group of TIE1 had a higher frequency of mutations in TP53 and ARID1, while the TMB score was lower. Conclusion: TIE1 might be an oncogene via regulating dysregulated immune infiltration to cause immunosuppression in GC and could be identified as a biomarker for prognosis and a therapeutic target for GC.