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Differential expression of microRNAs in preneoplastic gastric mucosa.

Link A, Schirrmeister W, Langner C, Varbanova M, Bornschein J, Wex T, Malfertheiner P - Sci Rep (2015)

Bottom Line: Gastric normal mucosa shows a unique expression pattern for miR-21, miR-155 and miR-223, which is specific for different regions.Using miRNA expression we calculated a score that allowed us to discriminate patients with AG from subjects with normal mucosa with high diagnostic accuracy in testing and validation cohorts reproducibly.However, differences of miRNA expression between the gastric antrum and the corpus need to be considered in future studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.

ABSTRACT
Gastric carcinogenesis is a multifactorial H.pylori-triggered dynamic process that goes through a cascade of preneoplastic conditions. The expression of miRNAs in the stomach with regard to preneoplastic precursor conditions and H.pylori infection has not been investigated systematically. In this prospective proof-of-principle study, we evaluated the miRNA expression in gastric antrum and corpus mucosa from patients with chronic non-atrophic gastritis (CNAG), atrophic gastritis (AG), and GC compared to controls. Gastric normal mucosa shows a unique expression pattern for miR-21, miR-155 and miR-223, which is specific for different regions. In correlation with progression of Correa's cascade and H.pylori infection, we observed a gradual increase in miR-155 and miR-223 both in corpus and antrum and miR-21 only in the antrum mucosa. Using miRNA expression we calculated a score that allowed us to discriminate patients with AG from subjects with normal mucosa with high diagnostic accuracy in testing and validation cohorts reproducibly. In summary, the expression pattern of miRNAs in the gastric mucosa is gradually increased with progression of Correa's cascade and H.pylori infection, suggesting miRNAs as potential biomarkers for preneoplastic precursor conditions. However, differences of miRNA expression between the gastric antrum and the corpus need to be considered in future studies.

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Related in: MedlinePlus

miRNA expression alterations in chronic gastritis and preneoplastic mucosal conditions.The expression of miR-21, miR-155 and miR-223 is shown as 2ΔdCt-values normalized to RNU6b for corpus (A–C) and antrum (D–F), respectively. N – controls (n = 19); CNAG – chronic non-atrophic gastritis (n = 25); AG – atrophic gastritis (n = 20); GC- tumor free antrum (n = 16) or corpus (n = 14) tissue from patients with gastric cancer. ***-p < 0.0001; **-p < 0.001; *- p < 0.05.
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f2: miRNA expression alterations in chronic gastritis and preneoplastic mucosal conditions.The expression of miR-21, miR-155 and miR-223 is shown as 2ΔdCt-values normalized to RNU6b for corpus (A–C) and antrum (D–F), respectively. N – controls (n = 19); CNAG – chronic non-atrophic gastritis (n = 25); AG – atrophic gastritis (n = 20); GC- tumor free antrum (n = 16) or corpus (n = 14) tissue from patients with gastric cancer. ***-p < 0.0001; **-p < 0.001; *- p < 0.05.

Mentions: There are only few studies available that evaluate the association of miRNA expression with mucosal changes in subjects with chronic gastritis. We looked at miRNA expression in relation to various pathological conditions of the gastric mucosa (including GC) in a well characterized prospectively collected cohort of samples (Table 1). As demonstrated in Figure 2, we did not find a significant difference in miR-21 expression in the corpus mucosa among the groups. The expression of miR-155 and miR-223 showed a stepwise increase from normal H.pylori-negative gastric mucosa to CNAG, AG and corpus mucosa from patients with GC (Figure 2A-C). The biggest increase in expression was observed in mucosa with AG while only non-significant changes were found between AG and corpus mucosa from GC patients. Similarly, expression of miR-21, miR-155 and miR-223 showed an increase from normal to CNAG, AG and GC antrum mucosa (Figure 2D–F). With respect to regional differences in the miRNA expression, miRNA expression in both corpus and antrum did not differ significantly between patients with preneoplastic conditions and mucosa from GC patients (Figure 2).


Differential expression of microRNAs in preneoplastic gastric mucosa.

Link A, Schirrmeister W, Langner C, Varbanova M, Bornschein J, Wex T, Malfertheiner P - Sci Rep (2015)

miRNA expression alterations in chronic gastritis and preneoplastic mucosal conditions.The expression of miR-21, miR-155 and miR-223 is shown as 2ΔdCt-values normalized to RNU6b for corpus (A–C) and antrum (D–F), respectively. N – controls (n = 19); CNAG – chronic non-atrophic gastritis (n = 25); AG – atrophic gastritis (n = 20); GC- tumor free antrum (n = 16) or corpus (n = 14) tissue from patients with gastric cancer. ***-p < 0.0001; **-p < 0.001; *- p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317705&req=5

f2: miRNA expression alterations in chronic gastritis and preneoplastic mucosal conditions.The expression of miR-21, miR-155 and miR-223 is shown as 2ΔdCt-values normalized to RNU6b for corpus (A–C) and antrum (D–F), respectively. N – controls (n = 19); CNAG – chronic non-atrophic gastritis (n = 25); AG – atrophic gastritis (n = 20); GC- tumor free antrum (n = 16) or corpus (n = 14) tissue from patients with gastric cancer. ***-p < 0.0001; **-p < 0.001; *- p < 0.05.
Mentions: There are only few studies available that evaluate the association of miRNA expression with mucosal changes in subjects with chronic gastritis. We looked at miRNA expression in relation to various pathological conditions of the gastric mucosa (including GC) in a well characterized prospectively collected cohort of samples (Table 1). As demonstrated in Figure 2, we did not find a significant difference in miR-21 expression in the corpus mucosa among the groups. The expression of miR-155 and miR-223 showed a stepwise increase from normal H.pylori-negative gastric mucosa to CNAG, AG and corpus mucosa from patients with GC (Figure 2A-C). The biggest increase in expression was observed in mucosa with AG while only non-significant changes were found between AG and corpus mucosa from GC patients. Similarly, expression of miR-21, miR-155 and miR-223 showed an increase from normal to CNAG, AG and GC antrum mucosa (Figure 2D–F). With respect to regional differences in the miRNA expression, miRNA expression in both corpus and antrum did not differ significantly between patients with preneoplastic conditions and mucosa from GC patients (Figure 2).

Bottom Line: Gastric normal mucosa shows a unique expression pattern for miR-21, miR-155 and miR-223, which is specific for different regions.Using miRNA expression we calculated a score that allowed us to discriminate patients with AG from subjects with normal mucosa with high diagnostic accuracy in testing and validation cohorts reproducibly.However, differences of miRNA expression between the gastric antrum and the corpus need to be considered in future studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.

ABSTRACT
Gastric carcinogenesis is a multifactorial H.pylori-triggered dynamic process that goes through a cascade of preneoplastic conditions. The expression of miRNAs in the stomach with regard to preneoplastic precursor conditions and H.pylori infection has not been investigated systematically. In this prospective proof-of-principle study, we evaluated the miRNA expression in gastric antrum and corpus mucosa from patients with chronic non-atrophic gastritis (CNAG), atrophic gastritis (AG), and GC compared to controls. Gastric normal mucosa shows a unique expression pattern for miR-21, miR-155 and miR-223, which is specific for different regions. In correlation with progression of Correa's cascade and H.pylori infection, we observed a gradual increase in miR-155 and miR-223 both in corpus and antrum and miR-21 only in the antrum mucosa. Using miRNA expression we calculated a score that allowed us to discriminate patients with AG from subjects with normal mucosa with high diagnostic accuracy in testing and validation cohorts reproducibly. In summary, the expression pattern of miRNAs in the gastric mucosa is gradually increased with progression of Correa's cascade and H.pylori infection, suggesting miRNAs as potential biomarkers for preneoplastic precursor conditions. However, differences of miRNA expression between the gastric antrum and the corpus need to be considered in future studies.

Show MeSH
Related in: MedlinePlus