Department of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Dig Dis Sci. 2020 Dec;65(12):3493-3501. doi: 10.1007/s10620-020-06096-7. Epub 2020 Jan 23.
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.
To investigate exosomal miRNAs as potential biomarkers of FD using liquid biopsy.
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).
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).
Exosomal hsa-miR-933 in gastric juice could be a candidate biomarker for FD.
外泌体中的 microRNAs(miRNAs)代表疾病特异性谱,并被应用于肿瘤学中的生物标志物。然而,在功能性消化不良(FD)中,外泌体 miRNAs 的作用尚未完全阐明。
通过液体活检研究外泌体 miRNAs 是否可作为 FD 的潜在生物标志物。
本回顾性队列研究纳入 11 例 FD 患者和 11 例年龄和性别匹配的健康对照者(HCs)。我们收集了胃分泌物并分离了外泌体 miRNAs。在发现队列中,通过 3D-Gene 微阵列评估了 2565 种 miRNAs 的表达水平。通过两种归一化方法(1)全局归一化和(2)通过内参归一化,比较 FD 患者和 HCs 外泌体中 miRNAs 的表达谱。随后,在验证队列中,通过定量逆转录 PCR(RT-qPCR)验证了 miRNAs 的表达水平。
通过两种方法的微阵列分析,我们鉴定出与 HCs 相比,FD 患者中 39 种 miRNAs 持续显著下调。其中,12 种 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 和 hsa-miR-3654)通过 RT-qPCR 进一步得到验证。我们的结果表明,与 HCs 相比,FD 中 hsa-miR-933 显著下调(0.317±0.205 倍,P=0.0317)。此外,hsa-miR-933 的表达水平与消化不良评分以及上腹痛和/或烧灼感的频率呈负相关(P<0.01,r=-0.835;P=0.0280,r=-0.688)。
胃分泌物中外泌体 hsa-miR-933 可能是 FD 的候选生物标志物。