Upregulation of THBS1 is Related to Immunity and Chemotherapy Resistance in Gastric Cancer

Abstract

Purpose Thrombospondin 1 (THBS1) is an endogenous inhibitor of angiogenesis, but it also promotes tumor invasion, metastasis, and immune response in the tumor environment. Previous research has found that THBS1 is highly expressed in many tumors and has a negative correlation with tumor prognosis. However, research on the relationship between THBS1 and immune infiltration in GC is less well documented, and the objective of our study was to investigate the role of THBS1 expression in GC. Patients and Methods The expression of THBS1 in GC was analyzed by Oncomine, TIMER, TGCA, GEO and IHC staining. Analysis of the signaling pathways associated with THBS1 expression in GC uses GSEA. The relationship between THBS1 expression and immune infiltration was analyzed by the ESTIMATE algorithm, single-cell transcriptome analysis, TIMER2 database and CIBERSORT algorithm. Finally, the relationship between THBS1 expression and drug sensitivity was analyzed by the CellMiner database. Results THBS1 was overexpressed in GC and was associated with poor prognosis, and high THBS1 expression was an independent risk factor. GSEA results showed that high THBS1 expression in GC was associated with tumorigenesis, adhesion, and significant immune enrichment. THBS1 expression was most strongly correlated with tumor-associated macrophages (TAMs), M2 macrophages and cancer-associated fibroblast (CAFs) in GC. THBS1 expression positively correlates with most immune checkpoint members, suggesting that THBS1 may play an important role in the tumor microenvironment. THBS1 overexpression was negatively correlated with some drug sensitivities, such as Oxaliplatin. Conclusion Upregulation of THBS1 was positively correlated with poor prognosis and immunosuppression in GC and negatively correlated with anticancer drug sensitivity, suggesting that THBS1 may serve as a potential target for the treatment of GC.