Effects of Thymidine Phosphorylase and Sine Oculis Homeobox Homologue 1 on the Prognosis and Immune Microenvironment of Gastric Cancer

Abstract

Objective

To investigate the combined effects of thymidine phosphorylase (TYMP) and sine oculis homeobox homologue 1 (Six1) on the tumor microenvironment and their role in promoting metastasis in gastric cancer (GC).

Methods

A total of 674 GC patients who underwent surgical resection were enrolled. Correlations between TYMP/Six1 expression and the clinicopathological characteristics and overall survival of patients were analysed. The expression of TYMP, Six1 and vascular endothelial growth factor C (VEGFc) was quantified via immunohistochemistry and quantitative real-time polymerase chain reaction. Cell transfection, wound-healing assays and bioinformatics analyses were used to explore the potential underlying mechanisms involved.

Results

Compared with the other groups, the Six1+ /TYMP+ patients exhibited poor differentiation, advanced tumor stage, a higher rate of lymphatic vessel invasion and shorter survival. Additionally, the protein expression of TYMP and Six1 was positively correlated with the VEGFc level. A significant increase in VEGFc expression was observed in cells transfected with TYMP, Six1, and TYMP/Six1 vectors. The results of the wound-healing assay indicated that the synergistic effect of TYMP and Six1 enhanced the migratory ability of GC cells. Furthermore, bioinformatics analysis revealed that TYMP and Six1 were positively correlated with immunosuppressive immune cell subsets and elevated the expression of inhibitory immune checkpoints in GC.

Conclusions

The combination of TYMP and Six1 is a good predictive and prognostic biomarker for GC. This combination enhances the expression of VEGFc, facilitates the invasion of GC cells, and may be linked to inhibitory immune cells and the tumor immune microenvironment.

Keywords

Gastric cancer / Metastasis / Prognosis / Immune checkpoints / Biomarkers

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Funding

National Natural Science Foundation of China(81602104)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to Huazhong University of Science and Technology