title: Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells.
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.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do 463-707, South Korea.
authors.forename: Yoon Jin
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do 463-707, South Korea, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea, nayoungkim49@empas.com.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do 463-707, South Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Chang
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do 463-707, South Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju 362-711, South Korea.
authors.forename: Seon Mee
authors.initials: SM
authors.lastname: Park
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do 463-707, South Korea.
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Shin
authors.affiliation: Department of Microbiology, College of Medicine, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Jung Mogg
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea.
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do 463-707, South Korea, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea.
authors.forename: Hyun Chae
authors.initials: HC
authors.lastname: Jung
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications* / Q000821:virology; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D018960:Hyaluronan Receptors; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D015820:Cadherins; D018960:Hyaluronan Receptors; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D051879:Twist-Related Protein 1; D014746:Vimentin