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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

Validation analyses of differential miRNA expression and receiver operating characteristics.(A) ΔCt-values for each miR-21, miR-155, and miR-223 were summarized to calculate the ∑ ΔCt-values for normal cohort (N; n = 19), for patients with atrophic gastritis from the first cohort (AG1; n = 20) and for the validation cohort (AG2; n = 21) from the antrum mucosa. (B) Receiver operating characteristics were calculated for the second cohort of patients with histologically confirmed atrophic gastritis using various summary scores. ***-p < 0.0001.
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f5: Validation analyses of differential miRNA expression and receiver operating characteristics.(A) ΔCt-values for each miR-21, miR-155, and miR-223 were summarized to calculate the ∑ ΔCt-values for normal cohort (N; n = 19), for patients with atrophic gastritis from the first cohort (AG1; n = 20) and for the validation cohort (AG2; n = 21) from the antrum mucosa. (B) Receiver operating characteristics were calculated for the second cohort of patients with histologically confirmed atrophic gastritis using various summary scores. ***-p < 0.0001.

Mentions: To validate the results to diagnostic accuracy, we analyzed an independent set of 21 antrum biopsies from patients with AG. As shown on the Figure 5, antral biopsies from patients with AG from the first cohort (AG1) and the independent validation cohort (AG2) showed both significantly higher miRNA ΣΔCt-value compared to samples from patients with normal mucosa (AG1: −10.97 ± 1.79 and AG2: −10.23 ± 3.78 vs. N: −15.69 ± 1.53, p < 0.0001). No differences were observed between AG1 and AG2. In the Figure 5B the calculations are presented in similar way as in Figure 4C and D. In similar fashion, the ROC curve analyses evaluating the miRNA expression ΣΔCt-value revealed an AUC of 0.9148 (95% CI 0.82 ± 1.010) for the independent cohort (AG2), which was similar to the first cohort, further supporting the diagnostic potential of miRNA expression analyses.


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)

Validation analyses of differential miRNA expression and receiver operating characteristics.(A) ΔCt-values for each miR-21, miR-155, and miR-223 were summarized to calculate the ∑ ΔCt-values for normal cohort (N; n = 19), for patients with atrophic gastritis from the first cohort (AG1; n = 20) and for the validation cohort (AG2; n = 21) from the antrum mucosa. (B) Receiver operating characteristics were calculated for the second cohort of patients with histologically confirmed atrophic gastritis using various summary scores. ***-p < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Validation analyses of differential miRNA expression and receiver operating characteristics.(A) ΔCt-values for each miR-21, miR-155, and miR-223 were summarized to calculate the ∑ ΔCt-values for normal cohort (N; n = 19), for patients with atrophic gastritis from the first cohort (AG1; n = 20) and for the validation cohort (AG2; n = 21) from the antrum mucosa. (B) Receiver operating characteristics were calculated for the second cohort of patients with histologically confirmed atrophic gastritis using various summary scores. ***-p < 0.0001.
Mentions: To validate the results to diagnostic accuracy, we analyzed an independent set of 21 antrum biopsies from patients with AG. As shown on the Figure 5, antral biopsies from patients with AG from the first cohort (AG1) and the independent validation cohort (AG2) showed both significantly higher miRNA ΣΔCt-value compared to samples from patients with normal mucosa (AG1: −10.97 ± 1.79 and AG2: −10.23 ± 3.78 vs. N: −15.69 ± 1.53, p < 0.0001). No differences were observed between AG1 and AG2. In the Figure 5B the calculations are presented in similar way as in Figure 4C and D. In similar fashion, the ROC curve analyses evaluating the miRNA expression ΣΔCt-value revealed an AUC of 0.9148 (95% CI 0.82 ± 1.010) for the independent cohort (AG2), which was similar to the first cohort, further supporting the diagnostic potential of miRNA expression analyses.

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