用沸石NaY上的蛋白质冠对血浆蛋白质组进行全面深入的分析。
Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY.
作者信息
Ma Congcong, Li Yanwei, Li Jie, Song Lei, Chen Liangyu, Zhao Na, Li Xueping, Chen Ning, Long Lixia, Zhao Jin, Hou Xin, Ren Li, Yuan Xubo
机构信息
Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300350, China.
Department of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital and Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
出版信息
J Pharm Anal. 2023 May;13(5):503-513. doi: 10.1016/j.jpha.2023.04.002. Epub 2023 Apr 12.
Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers. However, the vast dynamic range renders the profiling of proteomes extremely challenging. Here, we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY. Specifically, zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY (NaY-PPC), followed by conventional protein identification using liquid chromatography-tandem mass spectrometry. NaY was able to significantly enhance the detection of low-abundance plasma proteins, minimizing the "masking" effect caused by high-abundance proteins. The relative abundance of middle- and low-abundance proteins increased substantially from 2.54% to 54.41%, and the top 20 high-abundance proteins decreased from 83.63% to 25.77%. Notably, our method can quantify approximately 4000 plasma proteins with sensitivity up to pg/mL, compared to only about 600 proteins identified from untreated plasma samples. A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states. In summary, this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.
血浆的蛋白质组学表征对于新型药效学生物标志物的开发至关重要。然而,巨大的动态范围使得蛋白质组分析极具挑战性。在此,我们合成了沸石NaY,并开发了一种简单快速的方法,利用在沸石NaY上形成的血浆蛋白冠实现血浆蛋白质组的全面深度分析。具体而言,将沸石NaY与血浆共同孵育,在沸石NaY上形成血浆蛋白冠(NaY-PPC),随后使用液相色谱-串联质谱进行常规蛋白质鉴定。NaY能够显著增强低丰度血浆蛋白的检测,最大限度地减少高丰度蛋白引起的“掩盖”效应。中低丰度蛋白的相对丰度从2.54%大幅增加到54.41%,前20种高丰度蛋白从83.63%降至25.77%。值得注意的是,与从未经处理的血浆样品中鉴定出的约600种蛋白质相比,我们的方法能够以高达pg/mL的灵敏度定量约4000种血浆蛋白。一项基于30例肺腺癌患者和15名健康受试者血浆样本的初步研究表明,我们的方法能够成功区分健康状态和疾病状态。总之,这项工作为血浆蛋白质组学及其转化应用的探索提供了一个有利工具。