NDRG1 suppresses vasculogenic mimicry and tumor aggressiveness in gastric carcinoma

Xueyi Dong1,2, Yuheng Hong3, Huizhi Sun1

  • 1Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China.

Oncology Letters
|August 28, 2019
PubMed

Insights

N-myc downstream regulated gene 1 (NDRG1) suppresses metastasis in gastric carcinoma (GC) by inhibiting vasculogenic mimicry (VM) and epithelial-mesenchymal transition (EMT). This finding positions NDRG1 as a potential prognostic biomarker and therapeutic target for GC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis Research

Background:

  • N-myc downstream regulated gene 1 (NDRG1) is a known suppressor of metastasis in various carcinomas.
  • Vasculogenic mimicry (VM), driven by epithelial-mesenchymal transition (EMT), is a key factor in aggressive gastric carcinoma (GC) progression and therapeutic failure.
  • The role of NDRG1 in GC VM formation and its clinical significance remained largely uninvestigated.

Purpose of the Study:

  • To elucidate the function of NDRG1 in the formation of VM in gastric carcinoma (GC).
  • To investigate the correlation between NDRG1 expression and clinical outcomes in GC patients.
  • To explore the potential of NDRG1 as a prognostic biomarker and therapeutic target in GC.

Main Methods:

  • Immunohistochemistry was used to analyze NDRG1, VM-associated, and EMT-associated protein expression in 228 human GC samples.
  • Clinical significance was assessed, and data from 415 GC patients were analyzed using The Cancer Genome Atlas (TCGA) database.
  • Functional enrichment analyses were performed using Metascape and Gene Set Enrichment Analysis (GSEA).

Main Results:

  • NDRG1 expression was found to be negatively correlated with poor prognosis in GC.
  • NDRG1 significantly suppressed VM formation and decreased the expression of EMT-associated proteins.
  • HER2 expression was identified as potentially playing a significant role in NDRG1-mediated suppression of EMT.

Conclusions:

  • NDRG1 acts as a suppressor of VM formation in GC, correlating with improved prognosis.
  • NDRG1 negatively regulates EMT-associated protein expression, suggesting a mechanism for its anti-metastatic effect.
  • NDRG1 holds promise as a prognostic biomarker and a potential target for novel therapies in gastric carcinoma.

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