THBS2 is Closely Related to the Poor Prognosis and Immune Cell Infiltration of Gastric Cancer.

Shiyu Zhang,Li Liu,Huiying Yang,Guodu Tang,Huali Huang,Xuelian Xiang

doi:10.3389/fgene.2022.803460

Abstract

Background: The potential functions of Thrombospondin 2 (THBS2) in the progression and immune infiltration of gastric cancer (GC) remain unclear. The purpose of this study was to clarify the role of THBS2 in GC prognosis and the relationship between THBS2 and GC immune cell infiltration. Material and Methods: The differential expression levels of THBS2 in the GC and cancer-adjacent tissues were identified using the TCGA databases and verified using real-time polymerase chain reaction (PCR), immunohistochemical staining and two datasets from Gene Expression Omnibus (GEO). THBS2 related differential expressed genes (DEGs) were identified and used for further functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Furthermore, a THBS2-related immune infiltration analysis was also performed. Kaplan-Meier and Cox regression analyses were utilized to illustrate the effects of THBS2 on the prognosis and clinical variables of GC. Finally, a nomogram was constructed to predict the survival probability of patients with GC. Results: The THBS2 expression in GC was significantly higher than that in cancer-adjacent tissues (p < 0.001), which was verified using real-time PCR, immunohistochemical staining and datasets from GEO. The 599 identified DEGs were primarily enriched in pathways related to tumorigenesis and tumor progression, including the focal adhesion pathway, signaling by vascular endothelial growth factor, and Wnt signaling. THBS2 expression was positively correlated with the enrichment of the macrophages (r = 0.590, p < 0.001), which was also confirmed by immunohistochemistry; however, negatively correlated with the enrichment of Th17 cells (r = 0.260, p < 0.001). The high expression of THBS2 was significantly correlated with the pathological grade (p < 0.01), histological grade (p < 0.05), histological type (p < 0.05), T stage (p < 0.001), and poor overall survival (OS) (P = 0.003) of GC. The constructed nomogram can well predict the 1-, 3-, and 5-years OS probability of patients with GC (C-index [95% confidence interval] = 0.725 [0.701–0.750]). Conclusion: THBS2 is closely related to the poor prognosis and immune infiltration of gastric cancer.

Highlights

Gastric cancer (GC) is the fifth most common malignancy and the third most common cause of death globally (Park et al, 2018)
The 599 identified differential expressed genes (DEGs) were primarily enriched in pathways related to tumorigenesis and tumor progression, including the focal adhesion pathway, signaling by vascular endothelial growth factor, and Wnt signaling
THBS2 is closely related to the poor prognosis and immune infiltration of gastric cancer

Summary

Introduction

Gastric cancer (GC) is the fifth most common malignancy and the third most common cause of death globally (Park et al, 2018). Due to the improvement in endoscopic screening technology, in countries with a high incidence of GC, such as Japan and South Korea, more than 50 percent of GC patients can be diagnosed at an early stage (So et al, 2021). In most countries with poor screening technology, most patients are diagnosed at an advanced GC stage, which leads to poor treatment outcomes (Choi et al., 2015; Inokuchi et al, 2018). An in vitro study showed that THBS2 silencing inhibited the proliferation, migration and invasion of gastric. The potential functions of Thrombospondin 2 (THBS2) in the progression and immune infiltration of gastric cancer (GC) remain unclear. The purpose of this study was to clarify the role of THBS2 in GC prognosis and the relationship between THBS2 and GC immune cell infiltration

Objectives

Methods

Results

Discussion

Conclusion