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Follow-Up Study on CDX1 and CDX2 mRNA Expression in Noncancerous Gastric Mucosae After Helicobacter pylori Eradication

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Abstract

Background

Changes in CDX1/CDX2 in gastric mucosae following Helicobacter pylori eradication have not been clarified yet.

Aims

To evaluate the changes in CDX1/CDX2 expression after H. pylori eradication, in relation to the reversibility of intestinal metaplasia (IM).

Methods

Time course of CDX1/CDX2 expressions was investigated in 176 subjects with various gastroduodenal disorders. Among them, 132 patients were H. pylori positives; H. pylori were eradicated in 107 of them; 13 failed to eradicate; and 12 did not receive H. pylori eradication therapy. Forty-four subjects were H. pylori negatives. Expression levels in CDX1 and CDX2 from noncancerous gastric mucosae of the corpus, as well as the histologic findings of gastric mucosae, were evaluated during the follow-up.

Results

Average follow-up duration was 33.7 months (range 2–97 months). Expression levels in both CDX1 and CDX2 mRNAs were correlated with IM grade in the corpus (ρ = 0.633 and 0.554, respectively, all P < 0.001). Changes in CDX1/CDX2 mRNA expressions following H. pylori eradication showed only insignificant results; IM grade at the antrum and corpus showed a tendency to decrease after H. pylori eradication without statistical significance (P > 0.05). However, histologic improvement of IM at the corpus was associated with a decrease in CDX2 mRNA expression during the follow-up (linear mixed model, P for slope = 0.015).

Conclusions

In this study, eradication of H. pylori did not show any beneficial effects on aberrant CDX1/CDX2 expressions or IM. Reversibility of IM may be associated with a decrease in CDX2 mRNA expression.

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References

  1. Correa P. Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol. 1995;19:S37–S43.

    Article  PubMed  Google Scholar 

  2. Correa P, Shiao YH. Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res. 1994;54:1941s–1943s.

    CAS  PubMed  Google Scholar 

  3. Tucci A, Poli L, Tosetti C, et al. Reversal of fundic atrophy after eradication of Helicobacter pylori. Am J Gastroenterol. 1998;93:1425–1431.

    Article  CAS  PubMed  Google Scholar 

  4. Sung JJ, Lin SR, Ching JY, et al. Atrophy and intestinal metaplasia one year after cure of H. pylori infection: a prospective, randomized study. Gastroenterology. 2000;119:7–14.

    Article  CAS  PubMed  Google Scholar 

  5. Ohkusa T, Fujiki K, Takashimizu I, et al. Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated. Ann Intern Med. 2001;134:380–386.

    Article  CAS  PubMed  Google Scholar 

  6. Kang JM, Kim N, Shin CM, et al. Predictive factors for improvement of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication: a three-year follow-up study in Korea. Helicobacter. 2012;17:86–95.

    Article  PubMed  Google Scholar 

  7. Fukase K, Kato M, Kikuchi S, et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 2008;372:392–397.

    Article  PubMed  Google Scholar 

  8. Wong BC, Lam SK, Wong WM, et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004;291:187–194.

    Article  CAS  PubMed  Google Scholar 

  9. Silberg DG, Swain GP, Suh ER, et al. Cdx1 and cdx2 expression during intestinal development. Gastroenterology. 2000;119:961–971.

    Article  CAS  PubMed  Google Scholar 

  10. Suh E, Chen L, Taylor J, Traber PG. A homeodomain protein related to caudal regulates intestine-specific gene transcription. Mol Cell Biol. 1994;14:7340–7351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Silberg DG, Furth EE, Taylor JK, et al. CDX1 protein expression in normal, metaplastic, and neoplastic human alimentary tract epithelium. Gastroenterology. 1997;113:478–486.

    Article  CAS  PubMed  Google Scholar 

  12. Silberg DG, Sullivan J, Kang E, et al. Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice. Gastroenterology. 2002;122:689–696.

    Article  CAS  PubMed  Google Scholar 

  13. Almeida R, Silva E, Santos-Silva F, et al. Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. J Pathol. 2003;199:36–40.

    Article  PubMed  Google Scholar 

  14. Seno H, Oshima M, Taniguchi MA, et al. CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer: prognostic implications. Int J Oncol. 2002;21:769–774.

    CAS  PubMed  Google Scholar 

  15. Kim HS, Lee JS, Freund JN, et al. CDX-2 homeobox gene expression in human gastric carcinoma and precursor lesions. J Gastroenterol Hepatol. 2006;21:438–442.

    Article  CAS  PubMed  Google Scholar 

  16. Kang JM, Lee BH, Kim N, et al. CDX1 and CDX2 expression in intestinal metaplasia, dysplasia and gastric cancer. J Korean Med Sci. 2011;26:647–653.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Satoh K, Mutoh H, Eda A, et al. Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia: effect of eradication of Helicobacter pylori. Helicobacter. 2002;7:192–198.

    Article  CAS  PubMed  Google Scholar 

  18. Vauhkonen M, Vauhkonen H, Sipponen P. Helicobacter pylori infection induces a reversible expression of the CDX2 transcription factor protein in human gastric epithelium. Scand J Gastroenterol. 2008;43:915–921.

    Article  CAS  PubMed  Google Scholar 

  19. Kim SG, Jung HK, Lee HL, Korean College of Helicobacter and Upper Gastrointestinal Research, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. J Gastroenterol Hepatol. 2014;29:1371–1386.

    Article  PubMed  Google Scholar 

  20. Bair MJ, Wu MS, Chang WH, et al. Spontaneous clearance of Helicobacter pylori colonization in patients with partial gastrectomy: correlates with operative procedures and duration after operation. J Formos Med Assoc. 2009;108:13–19.

    Article  PubMed  Google Scholar 

  21. Shin CM, Kim N, Jung Y, et al. Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis. Cancer Sci. 2010;101:1337–1346.

    Article  CAS  PubMed  Google Scholar 

  22. Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161–1181.

    Article  CAS  PubMed  Google Scholar 

  23. Gelman A, Hill J. Data analysis using regression and multilevel/hierarchical models. New York: Cambridge University Press; 2007.

    Google Scholar 

  24. Bornschein J, Toth K, Selgrad M, et al. Dysregulation of CDX1, CDX2 and SOX2 in patients with gastric cancer also affects the non-malignant mucosa. J Clin Pathol. 2013;66:819–822.

    Article  PubMed  Google Scholar 

  25. Mutoh H, Sakurai S, Satoh K, et al. Cdx1 induced intestinal metaplasia in the transgenic mouse stomach: comparative study with Cdx2 transgenic mice. Gut. 2004;53:1416–1423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mutoh H, Sakurai S, Satoh K, et al. Development of gastric carcinoma from intestinal metaplasia in Cdx2-transgenic mice. Cancer Res. 2004;64:7740–7747.

    Article  CAS  PubMed  Google Scholar 

  27. Mutoh H, Hayakawa H, Sakamoto H, et al. Transgenic Cdx2 induces endogenous Cdx1 in intestinal metaplasia of Cdx2-transgenic mouse stomach. FEBS J. 2009;276:5821–5831.

    Article  CAS  PubMed  Google Scholar 

  28. Kim N, Park YS, Cho SI, et al. Prevalence and risk factors of atrophic gastritis and intestinal metaplasia in a Korean population without significant gastroduodenal disease. Helicobacter. 2008;13:245–255.

    Article  PubMed  Google Scholar 

  29. Ito M, Haruma K, Kamada T, et al. Helicobacter pylori eradication therapy improves atrophic gastritis and intestinal metaplasia: a 5-year prospective study of patients with atrophic gastritis. Aliment Pharmacol Ther. 2002;16:1449–1456.

    Article  CAS  PubMed  Google Scholar 

  30. Ley C, Mohar A, Guarner J, et al. Helicobacter pylori eradication and gastric preneoplastic conditions: a randomized, double-blind, placebo-controlled trial. Cancer Epidemiol Biomark Prev. 2004;13:4–10.

    Article  CAS  Google Scholar 

  31. Yang HB, Cheng HC, Sheu BS, Hung KH, Liou MF, Wu JJ. Chronic celecoxib users more often show regression of gastric intestinal metaplasia after Helicobacter pylori eradication. Aliment Pharmacol Ther. 2007;25:455–461.

    Article  CAS  PubMed  Google Scholar 

  32. Sheu BS, Tsai YC, Wu CT, et al. Long-term celecoxib can prevent the progression of persistent gastric intestinal metaplasia after H. pylori eradication. Helicobacter. 2013;18:117–123.

    Article  CAS  PubMed  Google Scholar 

  33. Correa P, Fontham ET, Bravo JC, et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy. J Natl Cancer Inst. 2000;92:1881–1888.

    Article  CAS  PubMed  Google Scholar 

  34. Zullo A, Rinaldi V, Hassan C, et al. Ascorbic acid and intestinal metaplasia in the stomach: a prospective, randomized study. Aliment Pharmacol Ther. 2000;14:1303–1309.

    Article  CAS  PubMed  Google Scholar 

  35. Xia HH, Talley NJ. Natural acquisition and spontaneous elimination of Helicobacter pylori infection: clinical implications. Am J Gastroenterol. 1997;92:1780–1787.

    CAS  PubMed  Google Scholar 

  36. Kang HY, Kim N, Park YS, et al. Progression of atrophic gastritis and intestinal metaplasia drives Helicobacter pylori out of the gastric mucosa. Dig Dis Sci. 2006;51:2310–2315.

    Article  PubMed  Google Scholar 

  37. Broussard CS, Goodman KJ, Phillips CV, et al. Antibiotics taken for other illnesses and spontaneous clearance of Helicobacter pylori infection in children. Pharmacoepidemiol Drug Saf. 2009;18:722–729.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Eda A, Osawa H, Yanaka I, et al. Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia. J Gastroenterol. 2002;37:94–100.

    Article  CAS  PubMed  Google Scholar 

  39. Shiotani A, Iishi H, Uedo N, et al. Helicobacter pylori-induced atrophic gastritis progressing to gastric cancer exhibits sonic hedgehog loss and aberrant CDX2 expression. Aliment Pharmacol Ther. 2006;24:71–80.

    Article  PubMed  Google Scholar 

  40. Lee JH, Kim N, Chung JI, et al. Long-term follow up of Helicobacter pylori IgG serology after eradication and reinfection rate of H. pylori in South Korea. Helicobacter. 2008;13:288–294.

    Article  CAS  PubMed  Google Scholar 

  41. Kato S, Matsukura N, Tsukada K, et al. Helicobacter pylori infection-negative gastric cancer in Japanese hospital patients: incidence and pathological characteristics. Cancer Sci. 2007;98:790–794.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant for the Global Core Research Center (GCRC) funded by the Korea government (MSIP, No. 2011-0030001), and by the Seoul National University Bundang Hospital Research Fund (Grant No. 02-2011-051).

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Correspondence to Nayoung Kim.

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Supplementary material 1 (TIFF 658 kb)

10620_2016_4048_MOESM2_ESM.tif

Supplementary Figure S2. Changes in CDX1 mRNA expression levels during the follow-up according to the improvement or aggravation of intestinal metaplasia (IM) grade at the corpus (n = 176). Histologic improvement of IM was associated with a decrease in CDX1 mRNA expression levels (A) and aggravation of IM with an increase of CDX1 mRNA levels (C), which was not statistically significant (P values for slope > 0.05) (TIFF 6627 kb)

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Shin, C.M., Kim, N., Chang, H. et al. Follow-Up Study on CDX1 and CDX2 mRNA Expression in Noncancerous Gastric Mucosae After Helicobacter pylori Eradication. Dig Dis Sci 61, 1051–1059 (2016). https://doi.org/10.1007/s10620-016-4048-y

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  • DOI: https://doi.org/10.1007/s10620-016-4048-y

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