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Background:  This study clarified the relationship between N-myc downstream regulated gene 1 (NDRG1) expression and the clinicopathological features, DNA methylation, prognosis and relevant signal pathways in gastric cancer (GC). Methods:  NDRG1 expression was examined by Western blot, immunohistochemistry and qRT-PCR. The clinical, transcriptome and methylation data of GC was downloaded from The Cancer Genome Atlas (TCGA), and extracted by R software. The overall survival (OS) rate of NDRG1 was analyzed by Kaplan- Meier plotter. The NDRG1-related gene set enrichment analysis (GSEA) was performed by GSEA-3.0.  Results:  NDRG1 expression was down-regulated at both mRNA and protein levels, and immunohistochemically correlated with tumor diameter, depth of invasion, lymph node metastasis and lymphatic invasion, tissue differentiation at a negative manner. The mRNA expression of NDRG1 was negatively related to its methylation. Kaplan-Meier plotter results indicated that NDRG1 was positively correlated with the prognosis of GC patients. NDRG1 was involved in cancer, Notch, PPAR, ERBB, adherens junction, and tight junction signal pathways. Conclusions:  In GC, NDRG1 expression was down-regulated, possibly due to DNA methylation. NDRG1 could play a role of tumor suppressor in the tumorigenesis by inhibiting multiple oncogenic signal pathways. The hypo-expression of NDRG1 was positively associated with malignant biological behavior and adverse prognosis in gastric cancer.

NDRG1 was downregulated and worked as favorable biomarker in the development of gastric cancer