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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.
Highlights
Based on the observation that the studied miRNAs are increased in gastric preneoplastic precursor conditions, we questioned if a simple and applicable miRNA expression score might have diagnostic potential and be useful for the risk stratification of patients with mucosal abnormalities
We combined DCt-values of the studied miRNAs into a single summary score for different combination of miRNAs with each other (DCtmiR-21 1 DCtmiR155 1 DCtmiR-223), creating the pooled miRNA expression score (SDCt-value, Figure 4A and B), which may facilitate the generation of individualized risk stratification
OLGA and OLGIM staging systems have been proposed for prediction of progression for gastric cancer development
Summary
The study protocol was approved by the Institutional Review Board of Otto-von-Guericke University Magdeburg (Number 80/11). Every participant gave his written informed consent prior to study inclusion. It would be further important to dissect this condition as it is frequently considered as ‘‘point of no return’’. In this proof-of-principle study, we focused on the expression of three selected miRNAs and additional studies are urgently needed to gain the global overview of miRNA expression changes and related epigenetic regulation such as DNA methylation[7]
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