Exosomal hsa-miR-3649 and hsa-miR-202-3p in Gastric Juice as Potential Biomarkers for Functional Dyspepsia with a Previous Helicobacter pylori Infection

Objective Specific microRNAs (miRNAs) in patients with functional dyspepsia (FD) and previous Helicobacter pylori (HP) infections have not been elucidated. This study aimed to investigate exosomal miRNAs as potential biomarkers of FD in patients with a previous HP infection using a liquid biopsy. Methods Six patients with FD and six age- and sex-matched healthy controls (HCs) with a previous HP infection were enrolled in the discovery cohort. Gastric juice and isolated exosomal miRNAs were collected. Subsequently, the expression of 2,565 miRNAs was evaluated by a microarray analysis, and FD-specific miRNAs were detected. Eight patients with FD and eight HCs were enrolled in the validation cohort. miRNA expression was validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results A microarray analysis identified five significantly downregulated miRNAs (hsa-miR-4738-3p, hsa-miR-5697, hsa-miR-8068, hsa-miR-3148, and hsa-miR-4521) and four significantly upregulated miRNAs (hsa-miR-3649, hsa-miR-451b, hsa-miR-202-3p, and hsa-miR-502-3p) in FD patients compared with HCs. In a validation study, three miRNAs were significantly upregulated in patients with FD (hsa-miR-3649, hsa-miR-202-3p, and hsa-miR-3148). The level of hsa-miR-3178 was inversely correlated with that observed in the discovery study. Furthermore, hsa-miR-3649 and hsa-miR-202-3p were significantly upregulated in patients with FD compared to HC (64.893±60.847-fold, p=0.0104; 14.906±15.022-fold, p=0.0379, respectively), and their expression was positively associated with the frequency of early satiation (p=0.0438, r=0.509; p=0.0256, r=0.555, respectively). Conclusion Exosomal hsa-miR-3649 and hsa-miR-202-3p may therefore be candidate biomarkers for FD in patients with previous HP infections.