Björkesten Johan, Enroth Stefan, Shen Qiujin, Wik Lotta, Hougaard David M, Cohen Arieh S, Sörensen Lene, Giedraitis Vilmantas, Ingelsson Martin, Larsson Anders, Kamali-Moghaddam Masood, Landegren Ulf
From the ‡Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
§Danish Center for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
Mol Cell Proteomics. 2017 Jul;16(7):1286-1296. doi: 10.1074/mcp.RA117.000015. Epub 2017 May 13.
An important motivation for the construction of biobanks is to discover biomarkers that identify diseases at early, potentially curable stages. This will require biobanks from large numbers of individuals, preferably sampled repeatedly, where the samples are collected and stored under conditions that preserve potential biomarkers. Dried blood samples are attractive for biobanking because of the ease and low cost of collection and storage. Here we have investigated their suitability for protein measurements. Ninety-two proteins with relevance for oncology were analyzed using multiplex proximity extension assays (PEA) in dried blood spots collected on paper and stored for up to 30 years at either +4 °C or -24 °C.Our main findings were that (1) the act of drying only slightly influenced detection of blood proteins (average correlation of 0.970), and in a reproducible manner (correlation of 0.999), (2) detection of some proteins was not significantly affected by storage over the full range of three decades (34 and 76% of the analyzed proteins at +4 °C and -24 °C, respectively), whereas levels of others decreased slowly during storage with half-lives in the range of 10 to 50 years, and (3) detectability of proteins was less affected in dried samples stored at -24 °C compared with at +4 °C, as the median protein abundance had decreased to 80 and 93% of starting levels after 10 years of storage at +4 °C or -24 °C, respectively. The results of our study are encouraging as they suggest an inexpensive means to collect large numbers of blood samples, even by the donors themselves, and to transport, and store biobanked samples as spots of whole blood dried on paper. Combined with emerging means to measure hundreds or thousands of protein, such biobanks could prove of great medical value by greatly enhancing discovery as well as routine analysis of blood biomarkers.
建立生物样本库的一个重要动机是发现能够在疾病早期、可能治愈阶段识别疾病的生物标志物。这需要来自大量个体的生物样本库,最好是进行重复采样,且样本的采集和存储条件要能保存潜在的生物标志物。干血样对生物样本库很有吸引力,因为其采集和存储简便且成本低。在此,我们研究了它们在蛋白质测量方面的适用性。使用多重邻位延伸分析(PEA)对92种与肿瘤学相关的蛋白质进行了分析,这些蛋白质来自采集在纸上并在4°C或-24°C下储存长达30年的干血斑。我们的主要发现是:(1)干燥过程对血液蛋白质检测的影响较小(平均相关性为0.970),且具有可重复性(相关性为0.999);(2)在三十年的整个时间段内,某些蛋白质检测不受存储的显著影响(分别在4°C和-24°C下,34%和76%的分析蛋白质),而其他蛋白质的水平在存储过程中缓慢下降,半衰期在10至50年之间;(3)与在4°C下储存的干样本相比,在-24°C下储存的干样本中蛋白质的可检测性受影响较小,因为在4°C或-24°C下储存10年后,蛋白质丰度中位数分别降至起始水平的80%和93%。我们的研究结果令人鼓舞,因为它们表明了一种低成本的方法来收集大量血样,甚至可以由捐赠者自己进行,并且可以将生物样本库样本作为全血干斑进行运输和存储。结合新兴的能够测量数百或数千种蛋白质的方法,这样的生物样本库通过极大地加强血液生物标志物的发现以及常规分析,可能会证明具有巨大的医学价值。