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

IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Miao Li, Wei Chen, Yao-Bing Chen, Lei Wang, Liu Huang
{"title":"Effects of Thymidine Phosphorylase and Sine Oculis Homeobox Homologue 1 on the Prognosis and Immune Microenvironment of Gastric Cancer.","authors":"Miao Li, Wei Chen, Yao-Bing Chen, Lei Wang, Liu Huang","doi":"10.1007/s11596-025-00065-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Medical Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11596-025-00065-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

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.

胸苷磷酸化酶和眼正弦同源盒同源物1对胃癌预后和免疫微环境的影响。
目的:探讨胸苷磷酸化酶(TYMP)和眼正弦同源盒同源物1 (Six1)在胃癌(GC)中对肿瘤微环境的影响及其促进转移的作用。方法:共纳入674例行手术切除的胃癌患者。分析TYMP/Six1表达与患者临床病理特征及总生存率的相关性。通过免疫组织化学和实时定量聚合酶链反应,定量检测TYMP、Six1和血管内皮生长因子C (VEGFc)的表达。细胞转染、伤口愈合试验和生物信息学分析被用来探索潜在的潜在机制。结果:与其他组相比,Six1+ /TYMP+患者分化差,肿瘤分期较晚,淋巴管浸润率较高,生存期较短。此外,TYMP和Six1的蛋白表达与VEGFc水平呈正相关。在转染TYMP、Six1和TYMP/Six1载体的细胞中,VEGFc表达显著增加。创面愈合实验结果显示TYMP和Six1的协同作用增强了胃癌细胞的迁移能力。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,并升高GC中抑制性免疫检查点的表达。结论:TYMP联合Six1是一种良好的预测胃癌预后的生物标志物。这种组合增强了VEGFc的表达,促进了GC细胞的侵袭,并可能与抑制性免疫细胞和肿瘤免疫微环境有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Current Medical Science
Current Medical Science Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.70
自引率
0.00%
发文量
126
期刊介绍: Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信