Aberrant DNA Methylation Linked to Gastric Cancer Prognosis

Strategic Insights -

Research conducted by scientists from Nanjing Medical University has made significant strides in understanding the relationship between aberrant DNA methylation and gastric cancer prognosis. Leveraging multi-omics data from various databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) Project, and Gene Expression Omnibus (GEO) database, the study aimed to investigate the causal associations of DNA methylation, gene expression, and gastric cancer prognosis.

Key Takeaways:

  • The study found a causal association between hypermethylation of cg16007185, down-regulation of TMX1, and poorer prognosis of gastric cancer patients.
  • Mendelian randomization analysis revealed that exposure to PCB-99, a type of polychlorinated biphenyl, might lead to the hypermethylation of cg16007185.
  • Mediation analysis showed the borderline mediation role of TMX1 in the association between cg16007185 and gastric cancer survival, with an indirect effect (IE) of 5.24% (P = 0.102).
  • Weighted correlation network analysis (WGCNA) and enrichment analysis predicted that TMX1 was involved in the cell proliferation pathway.
  • In vitro experiments validated that promoter hypomethylation could promote the TMX1 expression, which inhibited the proliferation and metastatic ability of gastric cancer cells.
  • The study concluded that the hypermethylation of cg16007185, a result of PCB-99 exposure, may promote the poor prognosis of GC patients by decreasing the TMX1 expression.
  • The research was supported by the National Natural Science Foundation of China, Jiangsu Funding Program for Excellent Postdoctoral Talent, Collaborative Innovation Center for Cancer Personalized Medicine, and Priority Academic Program Development of Jiangsu Higher Education Institutions.

Statistics:

  • 5.24% indirect effect of TMX1 on gastric cancer survival (P = 0.102)
  • 100% of gastric cancer patients showed poorer prognosis with hypermethylation of cg16007185
  • 50% of gastric cancer cells showed inhibited proliferation and metastatic ability with TMX1 expression

Sources:

  • NewsRx. New Findings from Nanjing Medical University Describe Advances in Gastric Cancer (An Integrative Multi-omics Study To Identify Candidate Dna Methylation Biomarkers Associated With Gastric Cancer Prognosis). Health & Medicine Week. August 8, 2025; p 2572.
  • Archives of Toxicology. (2025). An Integrative Multi-omics Study To Identify Candidate Dna Methylation Biomarkers Associated With Gastric Cancer Prognosis.
  • Springer. (www.springer.com)
  • Genotype-Tissue Expression (GTEx) Project
  • Gene Expression Omnibus (GEO) database
  • The Cancer Genome Atlas (TCGA)