DOI QR코드

DOI QR Code

Expression of the E-cadherin/β-catenin/tcf-4 Pathway in Gastric Diseases with Relation to Helicobacter pylori Infection: Clinical and Pathological Implications

  • Yu, Xiu-Wen (Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department) ;
  • Xu, Qian (Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department) ;
  • Xu, Ying (Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department) ;
  • Gong, Yue-Hua (Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department) ;
  • Yuan, Yuan (Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department)
  • Published : 2014.01.15

Abstract

Objective: To determine the expression of E-cadherin, ${\beta}$-catenin, and transcription factor 4 (TCF4) proteins in gastric diseases with relation to Helicobacter pylori infection. Methods: A total of 309 patients including 60 with superficial gastritis (SG), 57 with atrophic gastritis (AG) and 192 with gastric cancer (GC), were enrolled. The expression of E-cadherin, ${\beta}$-catenin, TCF4 proteins in the gastric mucosa was detected by immunohistochemistry and H. pylori infection by immunohistochemistry and PCR. Results: The expression rates of E-cadherin were significantly higher in SG and AG than in GC (P<0.01), while those of ${\beta}$-catenin in the nucleus were significantly lower in SG and AG than in GC (P<0.05). In GC cases, the expression rates of E-cadherin, ${\beta}$-catenin and TCF4 were significantly higher in the intestinal type than in the diffuse type (P<0.05). In GC patients, the expression rate of E-cadherin was significantly higher in the presence of H. pylori than in the absence of infection (P=0.011). Moreover, the expression level of TCF4 and ${\beta}$-catenin protein was significantly higher in the nucleus and cytoplasm in H. pylori positive than in H. pylori negative GC patients, especially in those with the intestinal type (all P < 0.05). Conclusion: The expression of E-cadherin and ${\beta}$-catenin progressively decreases during the process of GC tumorigenesis, while overexpression of TCF4 occurs. H. pylori infection is associated with a significant increase in the expression of E-cadherin and ${\beta}$-catenin in the cytoplasm and nucleus in GC patients, especially those with the intestinal type.

Keywords

References

  1. Aoki R, Yasuda M, Torisu R, et al (2007). Relationship between lymph node metastasis and E-cadherin expression in submucosal invasive gastric carcinomas with gastricphenotype. J Med Invest, 54, 159-67. https://doi.org/10.2152/jmi.54.159
  2. Bienz M, Clevers H (2000). Linking colorectal cancer to Wnt signaling. Cell, 103, 311-20. https://doi.org/10.1016/S0092-8674(00)00122-7
  3. Chelidonis G, Kavantzas N, Patsouris E, et al (2009). DNA ploidy, E-cadherin, beta-catenin expression and their clinicopathologic significance in imprints of non-small cell lung cancer. Anal Quant Cytol Histol, 31, 332-9.
  4. Correa P, Houghton J (2007). Carcinogenesis of Helicobacter pylori. Gastroenterology, 133, 659-72. https://doi.org/10.1053/j.gastro.2007.06.026
  5. Correa P, Piazuelo MB (2011). Helicobacter pylori infection and gastric adenocarcinoma. US Gastroenterol Hepatol Rev, 7, 59-64.
  6. Correa P, Piazuelo MB (2012). Evolutionary History of the Helicobacter pylori Genome: Implications for Gastric Carcinogenesis. Gut Liver, 6, 21-8. https://doi.org/10.5009/gnl.2012.6.1.21
  7. Ding SZ, Goldberg JB, Hatakeyama M (2010). Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis. Future Oncol, 6, 851-62. https://doi.org/10.2217/fon.10.37
  8. Dixon MF, Genta RM, Yardley JH, Correa P (1996). Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol, 20, 1161-81.
  9. Genta RM, Graham DY (1993). Intestinal metaplasia, not atrophy or achlorhydria, creates a hostile environment for Helicobacter pylori. Scand J Gastroenterol, 28, 924-8. https://doi.org/10.3109/00365529309103137
  10. Ilyas M (2005). Wnt signalling and the mechanistic basis of tumour development. J Pathol, 205, 130-44. https://doi.org/10.1002/path.1692
  11. Jin T, George Fantus I, Sun J (2008). Wnt and beyond Wnt: multiple mechanisms control the transcriptional property of beta-catenin. Cell Signal, 20, 1697-704. https://doi.org/10.1016/j.cellsig.2008.04.014
  12. Kavak E, Najafov A, Ozturk N, et al (2010). Analysis of the Wnt/B-catenin/TCF4 pathway using SAGE, genome-wide microarray and promoter analysis: Identification of BRI3 and HSF2 as novel targets. Cell Signal, 22, 1523-35. https://doi.org/10.1016/j.cellsig.2010.05.021
  13. Kim JH, Choi YJ, Lee SH, et al (2010). Effect of Helicobacter pylori infection on the sonic hedgehog signaling pathway in gastric cancer cells. Oncol Rep, 23, 1523-8.
  14. Kirikoshi H, Sekihara H, Katoh M (2001). Up-regulation of WNT10A by tumor necrosis factor alpha and Helicobacter pylori in gastric cancer. Int J Oncol, 19, 533-6.
  15. Kurashima Y, Murata-Kamiya N, Kikuchi K, et al (2008). Deregulation of beta-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence. Int J Cancer, 122, 823-31. https://doi.org/10.1002/ijc.23190
  16. Lauren P (1965). The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma -an attempt at a histo-clinical classification. Acta Pathol Microbiol Scand, 64, 31-49.
  17. Liu YE, Yu XW, Dong NN, et al (2008). The conditions of Helicobacter pylori colonization in different gastric diseases. Zhonghua Yi Xue Za Zhi, 88, 230-2 (in Chinese).
  18. Lu JJ, Perng CL, Shyu RY, et al (1999). Comparison of five PCR methods for detection of Helicobacter pylori DNA in gastric tissues. J Clin Microbiol, 37, 772-4.
  19. Macleod RJ (2012). MDR-1, Bcl-xL, H. pylori, and Wnt/betacatenin signalling in the adult stomach: how much is too much? Lab Invest, 92, 1670-3. https://doi.org/10.1038/labinvest.2012.151
  20. McMillan M, Kahn M (2005). Investigating Wnt signaling: a chemogenomic safari. Drug Discov Today, 10, 1467-74. https://doi.org/10.1016/S1359-6446(05)03613-5
  21. Nabais S, Machado JC, Lopes C, et al (2003). Patterns of betacatenin expression in gastric carcinoma: clinicopathological relevance and mutation analysis. Int J Surg Pathol, 11, 1-9. https://doi.org/10.1177/106689690301100102
  22. Neal JT, Peterson TS, Kent ML, Guillemin K (2013). H. pylori virulence factor CagA increases intestinal cell proliferation by Wnt pathway activation in a transgenic zebrafish model. Dis Model Mech, 6, 802-10. https://doi.org/10.1242/dmm.011163
  23. Ogasawara N, Tsukamoto T, Mizoshita T, et al (2006). Mutations and nuclear accumulation of beta-catenin correlate with intestinal phenotypic expression in human gastric cancer. Histopathology, 49, 612-21. https://doi.org/10.1111/j.1365-2559.2006.02560.x
  24. Osman MA, Bloom GS, Tagoe EA (2013). Helicobacter pyloriinduced alteration of epithelial cell signaling and polarity: a possible mechanism of gastric carcinoma etiology and disparity. Cytoskeleton (Hoboken), 70, 349-59. https://doi.org/10.1002/cm.21114
  25. Pagaki E, Patsouris E, Gonidi M, et al (2010). The value of E-cadherin/beta-catenin expression in imprints of NCSLC: relationship with clinicopathological factors. Diagn Cytopathol, 38, 419-24.
  26. Pandurangan AK (2013). Potential targets for prevention of colorectal cancer: a focus on PI3K/Akt/mTOR and Wnt pathways. Asian Pac J Cancer Prev, 14, 2201-5. https://doi.org/10.7314/APJCP.2013.14.4.2201
  27. Prasad CP, Rath G, Mathur S, et al (2009). Expression analysis of E-cadherin, Slug and GSK3beta in invasive ductal carcinoma of breast. BMC Cancer, 9, 325. https://doi.org/10.1186/1471-2407-9-325
  28. Riggio MP, Lennon A, Wray D (2000). Detection of Helicobacter pylori DNA in recurrent aphthous stomatitis tissue by PCR. J Oral Pathol Med, 29, 507-13. https://doi.org/10.1034/j.1600-0714.2000.291005.x
  29. Sibony M, Jones NL (2012). Recent advances in Helicobacter pylori pathogenesis. Curr Opin Gastroenterol, 28, 30-5. https://doi.org/10.1097/MOG.0b013e32834dda51
  30. Stolte M, Meining A (2001). The updated Sydney system: classification and grading of gastritis as the basis of diagnosis and treatment. Can J Gastroenterol, 15, 591-8.
  31. Tamura G (2008). Gastric cancer: histological type, histogenesis, and gene abnormalities. Gan To Kagaku Ryoho, 35, 343-9 (in Japanese).
  32. Thevenod F, Chakraborty PK (2010). The role of Wnt/betacatenin signaling in renal carcinogenesis: lessons from cadmium toxicity studies. Curr Mol Med, 10, 387-404. https://doi.org/10.2174/156652410791316986
  33. Tuynman JB, Vermeulen L, Boon EM, et al (2008). Cyclooxygenase-2 inhibition inhibits c-Met kinase activity and Wnt activity in colon cancer. Cancer Res, 68, 1213-20. https://doi.org/10.1158/0008-5472.CAN-07-5172
  34. Wang Q, Sun ZX, Allgayer H, Yang HS (2010a). Downregulation of E-cadherin is an essential event in activating beta-catenin/ Tcf-dependent transcription and expression of its target genes in Pdcd4 knockdown cells. Oncogene, 29, 128-38. https://doi.org/10.1038/onc.2009.302
  35. Wang Q, Symes AJ, Kane CA, et al (2010b). A novel role for Wnt/Ca2+ signaling in actin cytoskeleton remodeling and cell motility in prostate cancer. PloS One, 5, e10456. https://doi.org/10.1371/journal.pone.0010456
  36. Watanabe T, Asano N, Fichtner-Feigl S, et al (2010). NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway. J Clin Invest, 120, 1645-62. https://doi.org/10.1172/JCI39481
  37. Wu WK, Cho CH, Lee CW, et al (2010). Dysregulation of cellular signaling in gastric cancer. Cancer Lett, 295, 144-53. https://doi.org/10.1016/j.canlet.2010.04.025
  38. Yu XW, Xu Q, Gong YH, et al (2009). Detection in situ of E-cadherin, ${\beta}$-catenin, TCF4 and CDX2 in various gastric diseases. Chin J Cancer Res, 21, 185-93. https://doi.org/10.1007/s11670-009-0185-6
  39. Zhang C, Yamada N, Wu YL, et al (2005). Helicobacter pylori infection, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer and early gastric cancer. World J Gastroenterol, 11, 791-6. https://doi.org/10.3748/wjg.v11.i6.791

Cited by

  1. Prognostic Significance of Beta-Catenin Expression in Patients with Esophageal Carcinoma: a Meta-analysis vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6103
  2. Modified Toluidine Blue: an Alternative Stain for Helicobacter pylori Detection in Routine Diagnostic Use and Post-eradication Confirmation for Gastric Cancer Prevention vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6983
  3. Expression and significance of annexin A2 in patients with gastric adenocarcinoma and the association with E-cadherin vol.10, pp.2, 2015, https://doi.org/10.3892/etm.2015.2565
  4. EXPRESSION OF E-CADHERIN AND WNT PATHWAY PROTEINS BETACATENIN, APC, TCF-4 AND SURVIVIN IN GASTRIC ADENOCARCINOMA: CLINICAL AND PATHOLOGICAL IMPLICATION vol.29, pp.4, 2016, https://doi.org/10.1590/0102-6720201600040004
  5. Confirming the Effects of Qinghuayin against Chronic Atrophic Gastritis and a Preliminary Observation of the Involved Inflammatory Signaling Pathways: An In Vivo Study vol.2018, pp.1741-4288, 2018, https://doi.org/10.1155/2018/4905089
  6. Virulence Factor CagA and Ammonium Ion on Mucins in AGS Cells vol.59, pp.5, 2018, https://doi.org/10.3349/ymj.2018.59.5.633
  7. Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers vol.9, pp.1664-302X, 2018, https://doi.org/10.3389/fmicb.2018.00636