Skip to main content
Erschienen in: Digestive Diseases and Sciences 4/2016

01.04.2016 | Original Article

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

verfasst von: Cheol Min Shin, Nayoung Kim, Hyun Chang, Joo Sung Kim, Dong Ho Lee, Hyun Chae Jung

Erschienen in: Digestive Diseases and Sciences | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Correa P. Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol. 1995;19:S37–S43.CrossRefPubMed Correa P. Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol. 1995;19:S37–S43.CrossRefPubMed
2.
Zurück zum Zitat Correa P, Shiao YH. Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res. 1994;54:1941s–1943s.PubMed Correa P, Shiao YH. Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res. 1994;54:1941s–1943s.PubMed
3.
Zurück zum Zitat Tucci A, Poli L, Tosetti C, et al. Reversal of fundic atrophy after eradication of Helicobacter pylori. Am J Gastroenterol. 1998;93:1425–1431.CrossRefPubMed Tucci A, Poli L, Tosetti C, et al. Reversal of fundic atrophy after eradication of Helicobacter pylori. Am J Gastroenterol. 1998;93:1425–1431.CrossRefPubMed
4.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
5.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
6.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
7.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
8.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
9.
Zurück zum Zitat Silberg DG, Swain GP, Suh ER, et al. Cdx1 and cdx2 expression during intestinal development. Gastroenterology. 2000;119:961–971.CrossRefPubMed Silberg DG, Swain GP, Suh ER, et al. Cdx1 and cdx2 expression during intestinal development. Gastroenterology. 2000;119:961–971.CrossRefPubMed
10.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
12.
Zurück zum Zitat Silberg DG, Sullivan J, Kang E, et al. Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice. Gastroenterology. 2002;122:689–696.CrossRefPubMed Silberg DG, Sullivan J, Kang E, et al. Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice. Gastroenterology. 2002;122:689–696.CrossRefPubMed
13.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
14.
Zurück zum Zitat 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.PubMed 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.PubMed
15.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
16.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
18.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
19.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
20.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
21.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
22.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
23.
Zurück zum Zitat Gelman A, Hill J. Data analysis using regression and multilevel/hierarchical models. New York: Cambridge University Press; 2007. Gelman A, Hill J. Data analysis using regression and multilevel/hierarchical models. New York: Cambridge University Press; 2007.
24.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
25.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
27.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
28.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
29.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
30.
Zurück zum Zitat 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.CrossRef 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.CrossRef
31.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
32.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
33.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
34.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
35.
Zurück zum Zitat Xia HH, Talley NJ. Natural acquisition and spontaneous elimination of Helicobacter pylori infection: clinical implications. Am J Gastroenterol. 1997;92:1780–1787.PubMed Xia HH, Talley NJ. Natural acquisition and spontaneous elimination of Helicobacter pylori infection: clinical implications. Am J Gastroenterol. 1997;92:1780–1787.PubMed
36.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
37.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
39.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
40.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
41.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
Metadaten
Titel
Follow-Up Study on CDX1 and CDX2 mRNA Expression in Noncancerous Gastric Mucosae After Helicobacter pylori Eradication
verfasst von
Cheol Min Shin
Nayoung Kim
Hyun Chang
Joo Sung Kim
Dong Ho Lee
Hyun Chae Jung
Publikationsdatum
01.04.2016
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 4/2016
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-016-4048-y

Weitere Artikel der Ausgabe 4/2016

Digestive Diseases and Sciences 4/2016 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.