Ion exchange- and enrichment-based technology applied to large-scale plasma proteomic analysis of breast cancer neoadjuvant chemotherapy

IF 3.8 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography A Pub Date : 2025-03-27 DOI:10.1016/j.chroma.2025.465914

Xiaozhen Cui , Zhihua Zhong , Sen Xu , Yini Pan , Xi Wang , Luobin Zhang , An He , Xueting Ye , Hua Cao , Weibing Zhang , Ruijun Tian

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Abstract

Mass spectrometry (MS) based proteomics provides unbiased quantification of all proteins in plasma, which can dynamically reflect individual health states in real time. However, large-scale proteomics studies are constrained by the excessive dynamic range of plasma proteome and low throughput. Herein, two kinds of magnetic metal-organic frameworks (MOFs) modified with ion exchange functional groups (denoted as MHP-UiO-66-SAX and MHP-HKUST-1-SCX) were designed and fabricated to exhibit large protein adsorption capability, which were combined with an automated Liquid-handling System, thus realizing in-depth, high-throughput and automated proteomics studies. The constructed workflow could automatically complete the sample preparation before MS within only six hours and nearly a thousand protein groups per sample could be quantified. In the cohort study of nearly one hundred breast cancer neoadjuvant chemotherapy (NC) plasma samples, two differentially expressed proteins previously reported as biomarkers were related with the pathological complete response (PCR) of the breast cancer, demonstrating the feasibility of the developed technology for preparing large-scale clinical samples and exhibiting the potential application in monitoring the effect of chemotherapy.

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离子交换和富集技术应用于乳腺癌新辅助化疗的大规模血浆蛋白质组学分析

基于质谱（MS）的蛋白质组学提供了对血浆中所有蛋白质的无偏定量，可以实时动态地反映个体的健康状态。然而，大规模的蛋白质组学研究受到血浆蛋白质组动态范围过大和低通量的限制。本文设计并制备了两种离子交换功能基团修饰的磁性金属有机框架（mof），分别为MHP-UiO-66-SAX和MHP-HKUST-1-SCX，具有较大的蛋白质吸附能力，并与自动化液体处理系统相结合，实现了深入、高通量和自动化的蛋白质组学研究。构建的工作流程可在6小时内自动完成质谱前的样品制备，每个样品可定量近千个蛋白质组。在近100例乳腺癌新辅助化疗（NC）血浆样本的队列研究中，两种差异表达蛋白作为生物标志物与乳腺癌的病理完全反应（PCR）相关，证明了所开发的技术制备大规模临床样本的可行性，以及在化疗效果监测方面的潜在应用。

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来源期刊

Journal of Chromatography A 化学-分析化学

CiteScore

7.90

自引率

14.60%

发文量

742

审稿时长

45 days

期刊介绍： The Journal of Chromatography A provides a forum for the publication of original research and critical reviews on all aspects of fundamental and applied separation science. The scope of the journal includes chromatography and related techniques, electromigration techniques (e.g. electrophoresis, electrochromatography), hyphenated and other multi-dimensional techniques, sample preparation, and detection methods such as mass spectrometry. Contributions consist mainly of research papers dealing with the theory of separation methods, instrumental developments and analytical and preparative applications of general interest.