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中华普通外科学文献(电子版)

中华普通外科学文献(电子版) ›› 2026, Vol. 20 ›› Issue (04) : 238 -244. doi: 10.3877/cma.j.issn.1674-0793.2026.04.004

论著

Netrin-1通过上皮-间质转化促进胃腺癌恶性进展的研究
安杰1, 牛云峰1, 陈金辉2, 刘广超2, 张摇2, 刘伟2,†()   
  1. 1　050082　石家庄，中国人民解放军联勤保障部队第九八〇医院病理科
    2　050082　石家庄，中国人民解放军联勤保障部队第九八〇医院普外一科
  • 收稿日期:2025-08-30 出版日期:2026-08-01
  • 通信作者: 刘伟
  • 基金资助:
    河北省卫生健康委医学科学研究课题计划项目(20220247)

Study on Netrin-1 promoting malignant progression of gastric adenocarcinoma by epithelial-mesenchymal transition

Jie An1, Yunfeng Niu1, Jinhui Chen2, Guangchao Liu2, Yao Zhang2, Wei Liu2,†()   

  1. 1 Department of Pathology, the 980th Hospital of Joint Logistics Support Force of PLA, Shijiazhuang 050082, China
    2 Department of General Surgery, the 980th Hospital of Joint Logistics Support Force of PLA, Shijiazhuang 050082, China
  • Received:2025-08-30 Published:2026-08-01
  • Corresponding author: Wei Liu
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引用本文：

安杰, 牛云峰, 陈金辉, 刘广超, 张摇, 刘伟. Netrin-1通过上皮-间质转化促进胃腺癌恶性进展的研究[J/OL]. 中华普通外科学文献(电子版), 2026, 20(04): 238-244.

Jie An, Yunfeng Niu, Jinhui Chen, Guangchao Liu, Yao Zhang, Wei Liu. Study on Netrin-1 promoting malignant progression of gastric adenocarcinoma by epithelial-mesenchymal transition[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2026, 20(04): 238-244.

目的

探讨Netrin-1（NTN1）在胃腺癌中的表达情况，及其通过上皮-间质转化（EMT）参与胃腺癌的恶性进展机制。

方法

运用生物信息学对GSE49051数据集展开分析，探究NTN1在胃腺癌中的表达及功能富集。收集2022年6月至2024年6月64例胃腺癌及癌旁正常组织样本，借助实时荧光定量PCR（qPCR）与免疫组织化学染色检测NTN1表达程度，分析其与临床病理特征之间的关联。对NTN1进行敲低或过表达，运用细胞增殖实验（MTS法）、克隆形成实验、划痕愈合实验和Transwell侵袭实验，对胃腺癌细胞的增殖、迁移和侵袭能力展开评估，同时探究其对胃腺癌细胞中EMT相关标志物表达的影响。

结果

生物信息学分析显示，NTN1在胃腺癌组织中呈现高表达。基因本体论（GO）及京都基因和基因组数据库（KEGG）分析表明，NTN1参与细胞外基质形成、细胞迁移调控。qPCR与免疫组织化学检测结果显示，胃腺癌组织中NTN1表达显著高于癌旁正常组织，且与淋巴结转移、神经侵犯等病理特征相关。功能实验表明，敲低NTN1能够显著抑制胃腺癌细胞的增殖、迁移和侵袭能力，而过表达NTN1则增强上述行为。敲低NTN1可抑制胃腺癌细胞的EMT进程，具体表现为E-钙黏蛋白表达上调，波形蛋白、N-钙黏蛋白等间质标志物表达下调；反之，过表达NTN1则会推动EMT进程。

结论

NTN1在胃腺癌中呈现高表达，通过EMT参与胃腺癌的恶性进展。NTN1有望成为胃腺癌分子分型及靶向治疗的新型靶点，为研发新的治疗策略提供实验支撑。

关键词: Netrin-1, 胃腺癌, 上皮-间质转化, 恶性生物行为
Objective

To analyze the expression of Netrin-1 (NTN1) in gastric adenocarcinoma and investigate its role in triggering the epithelial-mesenchymal transition (EMT) process.

Methods

Bioinformatics analysis was conducted on the GSE49051 dataset to investigate the expression and functional enrichment of NTN1 in gastric adenocarcinoma. Sixty-four samples of gastric adenocarcinoma and adjacent normal tissues were collected, and the expression of NTN1 was detected by real-time fluorogenic quantitative PCR (qPCR) and immunohistochemical staining. The correlation between NTN1 expression and clinicopathological characteristics was analyzed. By knockdown or overexpression of NTN1, MTS assay, colony formation assay, wound healing assay, and Transwell invasion assay, the proliferation, migration, and invasion abilities of gastric adenocarcinoma cells were evaluated. Additionally, the effects of knockdown and overexpression of NTN1 on the expression of EMT-related markers in gastric adenocarcinoma cells were analyzed.

Results

Bioinformatics analysis showed that NTN1 was overexpressed in gastric adenocarcinoma tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that NTN1 was involved in biological processes such as extracellular matrix construction and cell migration regulation. qPCR and immunohistochemistry results showed that the expression of NTN1 in gastric adenocarcinoma tissues was significantly higher than that in adjacent normal tissues, and was closely correlated with pathological characteristics such as lymph node metastasis and nerve invasion. Functional experiments indicated that knocking down NTN1 significantly inhibited the proliferation, migration, and invasion abilities of gastric adenocarcinoma cells, while overexpressing NTN1 enhanced these abilities. Knockdown of NTN1 inhibited the EMT process in gastric adenocarcinoma cells, specifically manifested as increased expression of E-Cadherin and decreased expression of mesenchymal markers such as Vimentin and N-Cadherin. Conversely, overexpression of NTN1 promoted the EMT process.

Conclusions

NTN1 is overexpressed in gastric adenocarcinoma and intervenes in the malignant progression of gastric adenocarcinoma by the EMT process. NTN1 is expected to become a novel target for molecular typing and targeted therapy of gastric adenocarcinoma, providing substantial theoretical support for the development of new treatment strategies.

Key words: Netrin-1, Gastric adenocarcinoma, Epithelial-mesenchymal transition, Malignant biological behavior
图1 生物信息学显示Netrin-1（NTN1）在胃腺癌中表达情况　A为火山图用于展示胃腺癌（GSE49051数据集）与癌旁正常组织中基因的差异表达情况；B为基因本体论（GO）分析展示NTN1参与的生物学过程（BP）、分子功能（MF）及细胞组分（CC）；C为京都基因和基因组数据库（KEGG）通路富集图展示NTN1参与的信号通路；D为热图（Heatmap）通过颜色梯度直观展示NTN1在胃腺癌及正常胃组织样本中的表达模式
图2 Netrin-1（NTN1）在胃腺癌组织中表达情况及临床病理特征相关性　A为实时荧光定量PCR（qPCR）检测胃腺癌与癌旁正常组织中NTN1 mRNA表达；B为临床分期与NTN1表达相关性；C、D为qPCR及蛋白质印迹法（Western blotting）展示在胃腺癌细胞系中NTN1表达变化情况；E为免疫组织化学染色呈现NTN1蛋白在组织中的定位和表达情况
图3 敲低Netrin-1（NTN1）对胃腺癌细胞增殖、迁移及侵袭能力的影响　A、B展示了NTN1 shRNA的转染效率；C为转染NTN1 shRNA的MTS细胞增殖实验；D为转染NTN1 shRNA的克隆形成实验；E为转染NTN1 shRNA的划痕愈合实验；F为转染NTN1 shRNA的Transwell侵袭实验；**P<0.01
图4 过表达Netrin-1（NTN1）对胃腺癌细胞增殖、迁移及侵袭能力的影响　A、B展示了过表达NTN1的胃腺癌细胞转染效率；C为转染过表达NTN1的胃腺癌细胞MTS细胞增殖实验；D为转染过表达NTN1的胃腺癌细胞克隆形成实验；E为转染过表达NTN1的胃腺癌细胞划痕愈合实验；F为转染过表达NTN1的胃腺癌细胞Transwell侵袭实验；*P<0.05，**P<0.01
图5 Netrin-1（NTN1）对胃腺癌细胞的上皮-间充质转化进程的影响　E-钙黏蛋白（E-Cadherin）；波形蛋白（Vimentin）；N-钙黏蛋白（N-Cadherin）；基质金属蛋白酶2（MMP2）；**P<0.01
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