Exosomal hsa-miR-933 in Gastric Juice as a Potential Biomarker for Functional Dyspepsia
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ORIGINAL ARTICLE
Exosomal hsa‑miR‑933 in Gastric Juice as a Potential Biomarker for Functional Dyspepsia Fumio Tanaka1,2 · Shingo Takashima1 · Yuji Nadatani1,2 · Koji Otani1,2 · Shuhei Hosomi1 · Noriko Kamata1 · Koichi Taira1 · Yasuaki Nagami1 · Tetsuya Tanigawa1 · Shinya Fukumoto2 · Toshio Watanabe1 · Yoshiki Murakami3 · Norifumi Kawada2,4 · Yasuhiro Fujiwara1 Received: 30 August 2019 / Accepted: 20 January 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background MicroRNAs (miRNAs) in exosomes represent disease-specific profiles and are applied as biomarkers in oncology. However, in functional dyspepsia (FD), the role of exosomal miRNAs has not been fully elucidated. Aims To investigate exosomal miRNAs as potential biomarkers of FD using liquid biopsy. Methods This retrospective cohort study included 11 subjects with FD and 11 age- and sex-matched healthy controls (HCs). We collected gastric juice and isolated exosomal miRNAs. In a discovery cohort, expression levels of 2565 miRNAs were evaluated by 3D-Gene® microarray. miRNA expression profiles from exosomes of subjects with FD and HCs were compared by two normalization methods: (1) global normalization and (2) normalization by internal control. Subsequently, in a validation cohort, the expression levels of miRNAs were validated by quantitative reverse transcription PCR (RT-qPCR). Results Through microarray analysis using the two methods, we identified 39 miRNAs that were consistently and significantly downregulated in FD cases compared with those in HCs. Of these, 12 miRNAs (hsa-miR-933, hsa-miR-345-5p, hsa-miR-708-5p, hsa-miR-203a-3p, hsa-miR-619-5p, hsa-miR-4294, hsa-miR-4481, hsa-miR-196a-5p, hsa-miR-3918, hsamiR-372-3p, hsa-miR-658, and hsa-miR-3654) were further validated by RT-qPCR. Our results indicated that hsa-miR-933 was significantly downregulated in FD compared with HCs (0.317 ± 0.205-fold, P = 0.0317). Furthermore, the expression level of hsa-miR-933 was negatively associated with dyspepsia score and the frequency of epigastric pain and/or burning (P
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