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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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H.pylori infection and changes in miRNA expression in chronic gastritis patients.The expression of miR-21, miR-155 and miR-223 was evaluated in controls (N; n = 19), patients with chronic non-atrophic gastritis without evidence or present or past H.pylori infection (CNAG Hp-; n = 4) and patients with H.pylori positive gastritis (CNAG Hp+; n = 21). The values are presented as 2ΔdCt-values normalized to RNU6b for corpus (A–C) and antrum (D–F) separately. ***-p < 0.0001; **-p < 0.001; *- p < 0.05.
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f3: H.pylori infection and changes in miRNA expression in chronic gastritis patients.The expression of miR-21, miR-155 and miR-223 was evaluated in controls (N; n = 19), patients with chronic non-atrophic gastritis without evidence or present or past H.pylori infection (CNAG Hp-; n = 4) and patients with H.pylori positive gastritis (CNAG Hp+; n = 21). The values are presented as 2ΔdCt-values normalized to RNU6b for corpus (A–C) and antrum (D–F) separately. ***-p < 0.0001; **-p < 0.001; *- p < 0.05.

Mentions: H.pylori infection has been associated with alterations in the miRNA expression pattern21. Having shown a stepwise increase of the miRNA expression according to the stages of Correa's cascade, we questioned if these alterations might be related to H.pylori infection. Indeed, miR-155 and miR-223, both in corpus and antrum, were strongly elevated in patients with H.pylori-positive CNAG compared to controls (Figure 3). Although the miRNA expression was also slightly increased in the mucosa of H.pylori-negative CNAG the differences did not reach statistical significance. MiR-21 expression analyses revealed only a non-significant trend for increased expression in the antrum (p = 0.057) and no difference for the corpus (Figure 3A and D). Subgroupanalyses of H.pylori infection in patients with AG revealed only insignificant differences of miRNA expression between patients with and without H.pylori infection (data not shown), suggesting that mucosal alterations in later stages of Correa's cascade might be too advanced and probably not anymore dependent on H.pylori status in gastric mucosa.


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)

H.pylori infection and changes in miRNA expression in chronic gastritis patients.The expression of miR-21, miR-155 and miR-223 was evaluated in controls (N; n = 19), patients with chronic non-atrophic gastritis without evidence or present or past H.pylori infection (CNAG Hp-; n = 4) and patients with H.pylori positive gastritis (CNAG Hp+; n = 21). The values are presented as 2ΔdCt-values normalized to RNU6b for corpus (A–C) and antrum (D–F) separately. ***-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

f3: H.pylori infection and changes in miRNA expression in chronic gastritis patients.The expression of miR-21, miR-155 and miR-223 was evaluated in controls (N; n = 19), patients with chronic non-atrophic gastritis without evidence or present or past H.pylori infection (CNAG Hp-; n = 4) and patients with H.pylori positive gastritis (CNAG Hp+; n = 21). The values are presented as 2ΔdCt-values normalized to RNU6b for corpus (A–C) and antrum (D–F) separately. ***-p < 0.0001; **-p < 0.001; *- p < 0.05.
Mentions: H.pylori infection has been associated with alterations in the miRNA expression pattern21. Having shown a stepwise increase of the miRNA expression according to the stages of Correa's cascade, we questioned if these alterations might be related to H.pylori infection. Indeed, miR-155 and miR-223, both in corpus and antrum, were strongly elevated in patients with H.pylori-positive CNAG compared to controls (Figure 3). Although the miRNA expression was also slightly increased in the mucosa of H.pylori-negative CNAG the differences did not reach statistical significance. MiR-21 expression analyses revealed only a non-significant trend for increased expression in the antrum (p = 0.057) and no difference for the corpus (Figure 3A and D). Subgroupanalyses of H.pylori infection in patients with AG revealed only insignificant differences of miRNA expression between patients with and without H.pylori infection (data not shown), suggesting that mucosal alterations in later stages of Correa's cascade might be too advanced and probably not anymore dependent on H.pylori status in gastric mucosa.

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