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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

Regional differences in miRNA expression in the stomach mucosa.Expression of miR-21 (A), miR-155 (B) and miR-223 (C) were evaluated in paired corpus and antrum samples of the stomach (each n = 19). The values represent 2ΔdCt-values normalized to RNU6b. ***-p < 0.0001; scatter-plot, horizontal line represent medians.
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f1: Regional differences in miRNA expression in the stomach mucosa.Expression of miR-21 (A), miR-155 (B) and miR-223 (C) were evaluated in paired corpus and antrum samples of the stomach (each n = 19). The values represent 2ΔdCt-values normalized to RNU6b. ***-p < 0.0001; scatter-plot, horizontal line represent medians.

Mentions: Gastric biopsies or surgical specimens are frequently used for molecular analyses, however, the potential difference between the anatomical regions of the stomach has not been evaluated for miRNA expression yet. Therefore, we first compared the expression of miR-21, miR-155 and miR-223 in corpus and antrum samples from controls normal H.pylori-negative mucosa. All three studied miRNAs showed significantly lower expression in the antrum compared to the corpus mucosa in paired analyses. As shown in the Figure 1, the difference was more pronounced for miR-155 (corpus 0.02 ± 0.009 vs. antrum 0.006 ± 0.004) and for miR-223 (0.078 ± 0.05 vs. 0.02 ± 0.007) than for miR-21 (0.3 ± 0.08 vs. 0.22 ± 0.07). Similar expression patterns were observed in the mucosa of patients with chronic gastritis although the difference in the expression of miR-21 did not reach statistical significance (data not shown). Therefore, for further analyses, the miRNA expression was evaluated separately for different regions.


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)

Regional differences in miRNA expression in the stomach mucosa.Expression of miR-21 (A), miR-155 (B) and miR-223 (C) were evaluated in paired corpus and antrum samples of the stomach (each n = 19). The values represent 2ΔdCt-values normalized to RNU6b. ***-p < 0.0001; scatter-plot, horizontal line represent medians.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Regional differences in miRNA expression in the stomach mucosa.Expression of miR-21 (A), miR-155 (B) and miR-223 (C) were evaluated in paired corpus and antrum samples of the stomach (each n = 19). The values represent 2ΔdCt-values normalized to RNU6b. ***-p < 0.0001; scatter-plot, horizontal line represent medians.
Mentions: Gastric biopsies or surgical specimens are frequently used for molecular analyses, however, the potential difference between the anatomical regions of the stomach has not been evaluated for miRNA expression yet. Therefore, we first compared the expression of miR-21, miR-155 and miR-223 in corpus and antrum samples from controls normal H.pylori-negative mucosa. All three studied miRNAs showed significantly lower expression in the antrum compared to the corpus mucosa in paired analyses. As shown in the Figure 1, the difference was more pronounced for miR-155 (corpus 0.02 ± 0.009 vs. antrum 0.006 ± 0.004) and for miR-223 (0.078 ± 0.05 vs. 0.02 ± 0.007) than for miR-21 (0.3 ± 0.08 vs. 0.22 ± 0.07). Similar expression patterns were observed in the mucosa of patients with chronic gastritis although the difference in the expression of miR-21 did not reach statistical significance (data not shown). Therefore, for further analyses, the miRNA expression was evaluated separately for different regions.

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