Park Sungjin, Moon SeongRyeol, Lee Kiyoung, Park Ie Byung, Lee Dae Ho, Nam Seungyoon
Department of Genome Medicine and Science, Gachon University College of Medicine, Incheon, Republic of Korea.
Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, Republic of Korea.
Cell Physiol Biochem. 2018;46(4):1331-1340. doi: 10.1159/000489148. Epub 2018 Apr 18.
BACKGROUND/AIMS: Diabetic nephropathy (DN), a major diabetic microvascular complication, has a long and growing list of biomarkers, including microRNA biomarkers, which have not been consistent across preclinical and clinical studies. This meta-analysis aims to identify significant blood- and urine-incident microRNAs as diagnostic/prognostic biomarker candidates for DN.
PubMed, Web of Science, and Cochrane Library were searched from their earliest records through 12th Dec 2016. Relevant publications for the meta-analysis included (1) human participants; (2) microRNAs in blood and urine; (3) DN studies; and (4) English language. Four reviewers, including two physicians, independently and blindly extracted published data regarding microRNA profiles in blood and/or urine from subjects with diabetic nephropathy. A random-effect model was used to pool the data. Statistical associations between diabetic nephropathy and urinary or blood microRNA expression levels were assessed.
Fourteen out of 327 studies (n=2,747 patients) were selected. Blood or urinary microRNA expression data of diabetic nephropathy were pooled for this analysis. The hsa-miR-126 family was significantly (OR: 0.57; 95% CI: 0.44-0.74; p-value < 0.0001) downregulated in blood from patients with diabetic kidney disease, while its urinary level was upregulated (OR: 2931.12; 95% CI: 9.96-862623.21; p-value = 0.0059). The hsa-miR-770 family microRNA were significantly (OR: 10.24; 95% CI: 2.37-44.25; p-value = 0.0018) upregulated in both blood and urine from patients with diabetic nephropathy.
Our meta-analysis suggests that hsa-miR-126 and hsa-miR-770 family microRNA may have important diagnostic and pathogenetic implications for DN, which warrants further systematic clinical studies.
背景/目的：糖尿病肾病（DN）是一种主要的糖尿病微血管并发症，其生物标志物众多且不断增加，包括微小RNA生物标志物，但临床前和临床研究结果并不一致。本荟萃分析旨在确定显著的血液和尿液中出现的微小RNA，作为DN的诊断/预后生物标志物候选物。
检索了PubMed、Web of Science和Cochrane图书馆从最早记录到2016年12月12日的文献。纳入荟萃分析的相关出版物包括：（1）人类参与者；（2）血液和尿液中的微小RNA；（3）DN研究；（4）英文文献。四名评审员，包括两名医生，独立且盲法提取糖尿病肾病患者血液和/或尿液中微小RNA谱的已发表数据。采用随机效应模型汇总数据。评估糖尿病肾病与尿液或血液微小RNA表达水平之间的统计学关联。
从327项研究（n = 2747例患者）中筛选出14项。汇总了糖尿病肾病患者血液或尿液微小RNA表达数据进行分析。hsa-miR-126家族在糖尿病肾病患者血液中显著下调（OR：0.57；95% CI：0.44 - 0.74；p值 < 0.0001），而其尿液水平上调（OR：2931.12；95% CI：9.96 - 862623.21；p值 = 0.0059）。hsa-miR-770家族微小RNA在糖尿病肾病患者的血液和尿液中均显著上调（OR：10.24；95% CI：2.37 - 44.25；p值 = 0.0018）。
我们的荟萃分析表明，hsa-miR-126和hsa-miR-770家族微小RNA可能对DN具有重要的诊断和发病机制意义，值得进一步进行系统的临床研究。
