GBP1 Is a Prognostic Biomarker and Correlates With Immune Infiltrates in Gastric Cancer

Abstract

Background: The guanylate-binding protein 1 (GBP1) belongs to the member of GTPase dynamin superfamily and plays a major role as tumor suppressor or tumorigen in cancers, such as colon cancer, ovarian cancer, melanoma, and head and neck squamous cell carcinoma. However, the relationship between GBP1 and gastric cancer (GC) remains scanty. Methods: GBP1 mRNA expression in different types of tumors and their corresponding adjacent normal tissues were evaluated via exploring Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) database, while the protein expression was detected by The Human Protein Atlas (HPA). The relationship between the clinical characteristics and outcome of gastric cancer patients was examined through Kaplan–Meier plotter tool. The correlations between GBP1 and tumor immune infiltrates were evaluated via TIMER and TISIDB. Additionally, the relationship between GBP1 expression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA.Results: GBP1 expression was significantly higher in GC compared with corresponding normal tissues. High GBP1 expression in GC associated with better overall survival (OS HR=0.53, P=5.2e-09) and progression-free survival (PFS HR=0.49, P=1.90e-06). Moreover, its expression level was positively correlated with different clinical characteristics, such as sex, TNM stage, and Lauren classification. With a comprehensive analysis of three immune-related databases, TIMER, GEPIA, and TISIDB, we found GBP1 not only showed a strong correlation with tumor-infiltrating CD8+ T cells, Th1 cells, but also with Tregs, exhausted T cells, M2 macrophage, monocytes. Furthermore, GBP1 was significantly associated with IFN-γ, granzyme B, perforin, FasL and CXCL9, CXCL10, and CXCL11. Conclusion: This study provides the first evidence that GBP1 is a key gene that correlates with the prognosis and associated with various tumor-infiltrated immune cells in gastric cancer patients. In conclusion, GBP1 may act as a potent prognostic biomarker for predicting cancer progression and a sign of tumor-immune infiltration in GC.