Parker Victoria L, Gavriil Eleftherios, Marshall Benjamin, Pacey Allan, Heath Paul R
Department of Oncology and Metabolism, The University of Sheffield, Sheffield S10 2SF, United Kingdom.
Sheffield Institute of Translational Neuroscience, The University of Sheffield, Sheffield S10 2HQ, United Kingdom.
Biomed Rep. 2021 Feb;14(2):24. doi: 10.3892/br.2020.1400. Epub 2020 Dec 14.
Blood-derived microRNAs (miRNAs/miRs) are ideal clinical biomarkers, as they can be relatively non-invasively extracted and are stable across a range of storage conditions. However, the concentration and profile of miRNAs differ between specific patient groups and starting media, which must be a key consideration before embarking upon uses for clinical applications. The optimum blood-derived starting media for biomarker discovery involving pregnant women with an uncomplicated pregnancy has not been determined. Paired serum and plasma samples were collected from 10 pregnant women with uncomplicated low-risk pregnancies at three time points: i) During the second trimester of pregnancy; ii) during the third trimester; and iii) 6 weeks post-partum. Sample miRNA content was assessed using an Agilent Bioanalyzer Small RNA chip and reverse transcription-quantitative (RT-q)PCR using four constitutively expressed miRNAs: hsa-miR-222-3p, hsa-miR-23a, hsa-miR-30e-5p and hsa-miR-451a. Quality control spike-ins measured RNA extraction (UniSp2) and cDNA extraction (cel-miR-39-3p) efficiency. MiRNA concentration and percentage were significantly higher in the serum vs. plasma samples based on data obtained from the Bioanalyzer; however, RT-qPCR failed to replicate these differences in the majority of comparisons using the ΔCq values of the four constitutively expressed miRNAs. Using the standard deviations of the ΔCq values, the consistency of serum and plasma in terms of miRNA expression levels were equivalent. Thus, clinicians and researchers should take into consideration that different miRNA quantification methods can yield contrasting results with regards to the starting media utilized. Based on the equivalent performance of serum and plasma assessed using RT-qPCR, which is less likely to be influenced by the coagulation process or degraded long RNAs, both starting media assessed in the present study are equally suitable for ongoing biomarker discovery studies involving healthy pregnant women at any gestational time point or immediately postpartum.
血液来源的微小RNA(miRNA/miR)是理想的临床生物标志物,因为它们可以通过相对非侵入性的方式提取,并且在一系列储存条件下都很稳定。然而,特定患者群体和起始介质之间的miRNA浓度和谱存在差异,这在用于临床应用之前必须是一个关键考虑因素。尚未确定用于涉及无并发症妊娠孕妇的生物标志物发现的最佳血液来源起始介质。从10名无并发症低风险妊娠的孕妇在三个时间点收集配对的血清和血浆样本:i)妊娠中期;ii)妊娠晚期;iii)产后6周。使用安捷伦生物分析仪小RNA芯片和逆转录定量(RT-q)PCR,使用四种组成性表达的miRNA:hsa-miR-222-3p、hsa-miR-23a、hsa-miR-30e-5p和hsa-miR-451a评估样本miRNA含量。质量控制加标物测量RNA提取(UniSp2)和cDNA提取(cel-miR-39-3p)效率。根据生物分析仪获得的数据,血清中的miRNA浓度和百分比显著高于血浆样本;然而,在大多数使用四种组成性表达miRNA的ΔCq值的比较中,RT-qPCR未能重复这些差异。使用ΔCq值的标准差,血清和血浆在miRNA表达水平方面的一致性是等效的。因此,临床医生和研究人员应考虑到,不同的miRNA定量方法对于所使用的起始介质可能会产生截然不同的结果。基于使用RT-qPCR评估的血清和血浆的等效性能,RT-qPCR受凝血过程或降解的长RNA影响的可能性较小,本研究中评估的两种起始介质同样适用于涉及任何妊娠时间点或产后立即的健康孕妇的正在进行的生物标志物发现研究。