Li Miao, Chen Wei, Chen Yao-Bing, Wang Lei, Huang Liu
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.
Curr Med Sci. 2025 Jun 16. doi: 10.1007/s11596-025-00065-9.
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).
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.
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.
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.
探讨胸苷磷酸化酶（TYMP）和眼无同源盒1（Six1）对肿瘤微环境的联合影响及其在促进胃癌（GC）转移中的作用。
共纳入674例行手术切除的GC患者。分析TYMP/Six1表达与患者临床病理特征及总生存期的相关性。通过免疫组织化学和定量实时聚合酶链反应对TYMP、Six1和血管内皮生长因子C（VEGFc）的表达进行定量。采用细胞转染、伤口愈合试验和生物信息学分析来探讨潜在的相关机制。
与其他组相比，Six1+/TYMP+患者表现出低分化、肿瘤分期晚、淋巴管侵犯率高和生存期短。此外，TYMP和Six1的蛋白表达与VEGFc水平呈正相关。在用TYMP、Six1和TYMP/Six1载体转染的细胞中观察到VEGFc表达显著增加。伤口愈合试验结果表明，TYMP和Six1的协同作用增强了GC细胞的迁移能力。此外，生物信息学分析显示，TYMP和Six1与免疫抑制性免疫细胞亚群呈正相关，并提高了GC中抑制性免疫检查点的表达。
TYMP和Six1的联合是GC的良好预测和预后生物标志物。这种联合增强了VEGFc的表达，促进了GC细胞的侵袭，并且可能与抑制性免疫细胞和肿瘤免疫微环境有关。
