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

doi:10.3877/cma.j.issn.1674-0793.2026.04.004

Abstract

Abstract:

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

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]. Chinese Archives of General Surgery(Electronic Edition), 2026, 20(04): 238-244.

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URL: https://zhptwkxwx.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0793.2026.04.004

https://zhptwkxwx.cma-cmc.com.cn/EN/Y2026/V20/I04/238

Figures/Tables 5

References 22

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