Identification of miRNAs progressively deregulated in the biological model of gastric carcinogenesis

Abstract

Abstract Gastric adenocarcinoma is the result of the progression of preneoplastic lesions in gastric mucosa. Helicobacter pylori (H. pylori) infection is the main environmental risk factor linked to the multistep progression from precancerous conditions to gastric cancer. Identification of early diagnosis biomarkers in preneoplastic lesions could prevent progression to cancer. microRNAs (miRNAs) are non-coding RNAs that have emerged as promising candidates with diagnostic and prognostic potential. miRNAs differentially expressed and functional enrichment analysis were identified in miRNomes of gastric preneoplastic samples available at the European Nucleotide Archive (ENA) and in gastric adenocarcinoma samples from TCGA databases by limma-voom linear model on the Galaxy Collections platform and R package. The prognostic value of miRNAs was evaluated by Kaplan-Meier assays. The expression level of miR-18a-5p was determined by RT-qPCR in preneoplastic lesion samples from Mexican patients positive to pathogenic H. pylori and in the H. pylori-AGS cells co-cultures. Fifteen miRNAs were progressively deregulated in the multistep gastric carcinogenesis model, and they were predictors of the outcome in gastric adenocarcinoma patients. Additionally, miR-18a-5p was significantly upregulated in gastric tumors compared to normal gastric epithelium samples and it was also associated with better overall survival in GC patients. The expression of miR-18a-5p was significantly inhibited in gastric preneoplastic lesions positive to pathogenic H. pylori. Further, miR-18a-5p was up-regulated in AGS cells infected with pathogenic H. pylori strain. In conclusion, miRNAs signature distinguished the gastric lesions through malignant transformation process, including miR-18a-5p, which was exclusively associated with H. pylori infection.