Identification of serum microRNAs as potential diagnostic biomarkers for detecting precancerous lesions of gastric cancer

Abstract

Abstract Aim Gastric mucosal changes associated with chronic gastritis are known to be precancerous lesions of gastric cancer. We aimed to identify individuals with a high risk of gastric cancer by detection of microRNAs (miRNA) in the blood as biomarkers. Methods Of 1206 individuals screened, 144 who were positive for Helicobacter pylori (H. pylori) by the serum antibody test and who underwent endoscopy were the subjects of this study. For the gross assessment of mucosal inflammation, we applied the Kimura–Takemoto classification, in which normal mucosa was defined as grade 0, and atrophy was categorized as grade 1 (C‐1 and C‐2), grade 2 (C‐3 and O‐1), and grade 3 (O‐2 and O‐3). Serum samples were divided into two phases and used for miRNA microarray profiling. We compared the expression of miRNAs in grade 3 mucosa and other grades. Expression in gastric cancer was confirmed with TCGA data. Results miR‐196b‐3p was significantly upregulated, and miR‐92a‐2‐5p was downregulated (P < .05 and q < 0.2). TCGA data showed a high expression of miR‐196b‐3p in gastric cancer cases (P < .001). Comparing grade 3 and the others, the area under the receiver operating characteristic curve using the detected miRNAs was as high as about 0.7. Furthermore, the combination of miRNAs resulted in higher accuracy. In terms of the significance of the combinatory mRNAs, the combination of three miRNAs (miR‐196b‐3p, miR‐92a‐2‐5p, and miR‐6791‐3p) revealed high sensitivity and specificity, with the area under the curve exceeding 0.8. Conclusion The identified combinatory miRNAs may represent promising biomarkers of precancerous lesions in gastric cancer.

Keywords

• 3‐dimensional microarray
• gastric cancer
• Kimura–Takemoto classification
• miR‐196b
• precancerous lesion
• serum biomarker