Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells

Carcinogenesis. 2015 May;36(5):553-63. doi: 10.1093/carcin/bgv022. Epub 2015 Mar 16.

Abstract

We know little concerning the expression of transforming growth factor-β1 (TGF-β1) and TGF-β1-induced epithelial-mesenchymal transition (EMT) markers in gastric mucosa and their changes after eradication of Helicobacter pylori infection have not yet been clarified. In the present study, we compared the time course of messenger RNA (mRNA) expression of TGF-β1 and five EMT markers (Twist, Snail, Slug, vimentin and E-cadherin) in 111 controls, 55 patients with gastric dysplasia and 71 patients with early gastric cancer, following eradication of H.pylori. mRNA levels in non-cancerous gastric mucosa were measured using quantitative real time-polymerase chain reaction and the histologic findings of gastric mucosa were compared before and after eradication. The average duration of follow-up was 46.7 months (6.0-112.4). The levels of TGF-β1, Twist, Snail, Slug and vimentin mRNA, in addition to levels of CD44 detected by immunohistochemistry, showed all up-regulation in patients with dysplasia or early gastric cancer compared with controls (P < 0.05); moreover, the mRNA levels of E-cadherin, an epithelial marker, were decreased in these patients compared with the control group (P < 0.001). Eradication of H.pylori reduced the expression of TGF-β1, Twist, Snail, Slug and vimentin mRNA (P-value for slope <0.001), as well as the immunohistochemical expression of CD44 (P = 0.014), whereas it enhanced the expression of E-cadherin (P-value for slope < 0.05). Thus, H.pylori infection may trigger the TGF-β1-induced EMT pathway and the emergence of gastric cancer stem cells (CSCs). Its eradication may prevent the carcinogenesis of gastric cancer by inhibiting these two pathways.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Case-Control Studies
  • Epithelial-Mesenchymal Transition*
  • Female
  • Follow-Up Studies
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / pathology
  • Gene Expression Regulation, Neoplastic
  • Helicobacter Infections / complications*
  • Helicobacter Infections / virology
  • Helicobacter pylori / isolation & purification*
  • Humans
  • Hyaluronan Receptors
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Neoplastic Stem Cells / virology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Snail Family Transcription Factors
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / virology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • Biomarkers, Tumor
  • CD44 protein, human
  • Cadherins
  • Hyaluronan Receptors
  • Nuclear Proteins
  • RNA, Messenger
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TWIST1 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta1
  • Twist-Related Protein 1
  • Vimentin