Immunosuppressive microenvironment of TGIF1-overexpressing gastric cancers and its clinical significance

TONG Huyun; CHEN Xu; ZHANG Wenjie; WANG Tao; LI Xianfeng; QIU Qiu; WANG Bin

doi:10.16016/j.2097-0927.202508003

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Immunosuppressive microenvironment of TGIF1-overexpressing gastric cancers and its clinical significance

Basic Medicine | 更新时间：2025-12-25

- Immunosuppressive microenvironment of TGIF1-overexpressing gastric cancers and its clinical significance
- Journal of Army Medical University Vol. 47, Issue 20, Pages: 2451-2460(2025)
- 作者机构：
  
  1.陆军特色医学中心（第三军医大学大坪医院）消化内科，消化系统肿瘤精准防治重庆市重点实验室，重庆
  2.重庆大学医学院，重庆
  3.重庆市合川区人民医院消化内科，重庆
- 作者简介：
- 基金信息：
  
  the National Key Research and Development Program of China(2023YFC3402102;2022YFA1105302);the Project of Postgraduate Scientific Research Innovation of Chongqing(CYS25896)
- DOI：10.16016/j.2097-0927.202508003
  CLC： R181.23;R394.3;R735.2
- Received：01 August 2025，
  
  Revised：2025-10-11，
  
  Accepted：11 October 2025，
  
  Published：30 October 2025
- 稿件说明：
移动端阅览
童湖云，陈旭，张文杰，等.转录因子TGIF1高表达胃癌的免疫抑制性微环境特征及临床意义分析［J］.陆军军医大学学报，2025，47（20）：2451-2460.DOI：10.16016/j.2097-0927.202508003.

TONG H Y，CHEN X，ZHANG W J，et al.Immunosuppressive microenvironment of TGIF1-overexpressing gastric cancers and its clinical significance［J］.J Army Med Univ，2025，47（20）：2451-2460.DOI：10.16016/j.2097-0927.202508003.
童湖云，陈旭，张文杰，等.转录因子TGIF1高表达胃癌的免疫抑制性微环境特征及临床意义分析［J］.陆军军医大学学报，2025，47（20）：2451-2460.DOI：10.16016/j.2097-0927.202508003. DOI：

TONG H Y，CHEN X，ZHANG W J，et al.Immunosuppressive microenvironment of TGIF1-overexpressing gastric cancers and its clinical significance［J］.J Army Med Univ，2025，47（20）：2451-2460.DOI：10.16016/j.2097-0927.202508003. DOI：

摘要

目的

分析转录因子转化生长因子β诱导因子同源框1（TG-interacting factor 1， TGIF1）在胃癌中的表达水平及与胃癌患者预后相关性，研究TGIF1高表达胃癌的免疫微环境特征和临床意义。

方法

整合分析癌症基因组图谱（the Cancer Genome Atlas， TCGA）、亚洲癌症研究组织（Asian Cancer Research Group，ACRG）和本课题组建立的胃癌转录组数据库，结合免疫组化实验分析胃癌和正常胃黏膜组织TGIF1表达情况，分析Kaplan-Meier Plotter 在线数据库，探讨TGIF1表达与胃癌临床预后相关性。利用转录组数据分析TGIF1高表达胃癌的功能富集特征，通过GENIE3工具包预测TGIF1调控靶基因，STRING数据库推断蛋白-蛋白相互作用网络，探讨TGIF1可能调控的肿瘤免疫信号网络。结合单细胞转录组测序等技术分析TGIF1表达与胃癌微环境（tumor microenvironment，TME）紊乱的相关性。

结果

分析转录组数据表明TGIF1在胃癌组织显著高表达（

0.01），TGIF1高表达胃癌患者的临床预后较差（

0.05）。免疫组织化学染色发现TGIF1在胃癌组织中的表达显著高于正常组织（

0.01）。TGIF1高表达胃癌显著富集免疫调控信号通路，包含趋化因子配体20 （chemokine C-C motif ligand 20， CCL20）等一系列免疫抑制性细胞因子。TGIF1高表达胃癌具有免疫抑制性TME，富含免疫抑制性NK细胞、肥大细胞、调节性T细胞、髓系细胞和耗竭性CD8

T细胞。细胞互作分析发现，TGIF1高表达胃癌细胞可能通过CCL20识别调节性T细胞的CCR6受体，这两种互作细胞的特征性基因集高表达时，胃癌患者生存期显著缩短（

0.05）。

结论

TGIF1在胃癌组织中高表达，可能是免疫抑制性TME和临床不良预后的生物标志物，TGIF1高表达胃癌细胞可能与调节性T细胞等多种细胞互作，诱导TME免疫抑制状态。

Abstract

Objective

To determine the expression level of TG-interacting factor 1 (TGIF1) in gastric cancer (GC) and its correlation with prognosis

and investigate the characteristics of immune microenvironment of TGIF1-overexpressing GCs and its clinical significance.

Methods

Integrated analysis was performed using transcriptomic data from The Cancer Genome Atlas (TCGA)

Asian Cancer Research Group (ACRG)

and our in-house GC transcriptome database. Immunohistochemistry (IHC) assay was employed to compare TGIF1 expression between GC and normal gastric mucosa tissues. Based on Kaplan-Meier Plotter online database

the correlation between TGIF1 expression and clinical prognosis was evaluated. Transcriptomic data were analyzed to identify functional enrichment features of GC with high TGIF1 expression. The GENIE3 toolkit and STRING database were utilized to predict TGIF1-regulated target genes and protein-protein interaction (PPI) networks

respectively to explore the potential immune-related signaling pathways regulated by TGIF1. Single-cell RNA sequencing (scRNA-seq) was applied to analyze the association between TGIF1 expression and tumor microenvironment (TME) disorder.

Results

Transcriptomic analysis revealed significantly higher TGIF1 expression in GC tissues compared to normal tissues (

0.01). Patients with high TGIF1 expression exhibited poorer clinical prognosis (

0.05). IHC assay confirmed elevated TGIF1 expression in GC tissues than normal tissues (

0.01). GC with high TGIF1 expression was enriched in immune regulatory pathways

including immunosuppressive cytokines such as chemokine C-C motif ligand 20 (CCL20). These tumors displayed an immunosuppressive TME

characterized by abundant immunosuppressive NK cells

mast cells

regulatory T cells (Tregs)

myeloid cells

and exhausted CD8

T cells. Cell interaction analysis suggested that TGIF1-overexpressing GC cells may engage with Tregs

via

the CCL20-CCR6 axis. Co-high expression of signature gene sets from these interacting cells was associated with significantly shorter survival in the patients (

0.05).

Conclusion

TGIF1 is highly expressed in GC tissues and may serve as a biomarker for immunosuppressive TME and poor prognosis. TGIF1-overexpressing GC cells may interact with multiple immune cells

particularly Tregs

to induce an immunosuppressive microenvironment.

关键词

Keywords

references

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