S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Ph.D. / Sc.D._의학과)
The role of Helicobacter pylori on gastric carcinogenesis through epithelial-mesenchymal transition
헬리코박터 파일로리균이 상피-간엽전환을 통해 위암발생에 미치는 역할
- Yoon Jin Choi
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과 중개의학전공, 2016. 2. 김나영.
- 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 mRNA expression of TGF-β1 and 5 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 noncancerous gastric mucosa were measured using qRT-PCR 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 and Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) 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. Its eradication may prevent the carcinogenesis of gastric cancer by inhibiting these 2 pathways.