Expression of Demethylase Genes, FTO and ALKBH1, Is Associated with Prognosis of Gastric Cancer

Dig Dis Sci. 2019 Jun;64(6):1503-1513. doi: 10.1007/s10620-018-5452-2. Epub 2019 Jan 14.


Background: Reversible N6-methyladenosine (m6A) modifications in messenger RNAs can be categorized under the field of "RNA epigenetics." However, the potential role of m6A-related genes in gastric cancer (GC) prognosis has not been systematically researched.

Aims: This study was aimed at providing insights into the prognostic role of m6A-related gene expression, at both mRNA and protein levels.

Methods: Kaplan-Meier (KM) plotter database and The Cancer Genome Atlas (TCGA) database were used to explore the prognostic significance of individual m6A-related genes in overall survival (OS) and progression-free survival at the mRNA level. For independent validation, the protein level of genes significantly associated with prognosis in both databases was further detected in 450 paired GC and corresponding adjacent non-tumor tissues using tissue microarray (TMA)-based immunohistochemistry (IHC). The relationship between the FTO and ALKBH1 expression and the clinicopathological characteristics was explored.

Results: Among nine m6A-related genes, aberrantly high mRNA expression of FTO and ALKBH1 was associated with poor OS in the KM and TCGA cohorts. However, the TMA-IHC indicated that protein expression of FTO and ALKBH1 was markedly downregulated in GC tissues. A lower protein level of ALKBH1 was closely correlated with larger tumor sizes (≥ 5 cm) and more advanced TNM stages, while lower FTO protein expression was associated with shorter OS in GC patients.

Conclusions: Aberrant expression of demethylase genes, FTO and ALKBH1, has a distinct prognostic value in GC patients, indicating that FTO and ALKBH1 may play vital roles in GC progression and metastasis.

Keywords: ALKBH1; FTO; Gastric cancer; Prognostic values; Tissue microarray (TMA); m6A-related genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism
  • Aged
  • AlkB Homolog 1, Histone H2a Dioxygenase / genetics*
  • AlkB Homolog 1, Histone H2a Dioxygenase / metabolism
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics*
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Databases, Genetic
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Progression-Free Survival
  • RNA Processing, Post-Transcriptional
  • RNA Stability
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Risk Factors
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / therapy
  • Time Factors


  • Biomarkers, Tumor
  • RNA, Messenger
  • N-methyladenosine
  • ALKBH1 protein, human
  • AlkB Homolog 1, Histone H2a Dioxygenase
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • Adenosine