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Exosomal hsa-miR-933 in Gastric Juice as a Potential Biomarker for Functional Dyspepsia

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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, hsa-miR-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 < 0.01, r = − 0.835; P = 0.0280, r = − 0.688, respectively).

Conclusions

Exosomal hsa-miR-933 in gastric juice could be a candidate biomarker for FD.

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Acknowledgments

This work was supported by JSPS KAKENHI Grant Number JP16K09252. We thank the experimental support staff (Naomi Sakama, Emi Yoshioka, and Saori Itami) and nursing staff at MedCity21.

Funding

This work was supported by JSPS KAKENHI Grant Number JP16K09252.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    Fumio Tanaka, Shingo Takashima, Yuji Nadatani, Koji Otani, Shuhei Hosomi, Noriko Kamata, Koichi Taira, Yasuaki Nagami, Tetsuya Tanigawa, Toshio Watanabe & Yasuhiro Fujiwara

  2. Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Fumio Tanaka, Yuji Nadatani, Koji Otani, Shinya Fukumoto & Norifumi Kawada

  3. Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan

    Yoshiki Murakami

  4. Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Norifumi Kawada

Authors
  1. Fumio Tanaka
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  2. Shingo Takashima
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  14. Yasuhiro Fujiwara
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Correspondence to Fumio Tanaka.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee, and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The study protocol was approved by the ethics committee of the Osaka City University Graduate School of Medicine (protocol number 3438).

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Tanaka, F., Takashima, S., Nadatani, Y. et al. Exosomal hsa-miR-933 in Gastric Juice as a Potential Biomarker for Functional Dyspepsia. Dig Dis Sci 65, 3493–3501 (2020). https://doi.org/10.1007/s10620-020-06096-7

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  • DOI: https://doi.org/10.1007/s10620-020-06096-7

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