Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Department of Nephrology, Shenzhen Key Laboratory of Kidney Diseases, Shenzhen People's Hospital, (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, China.
J Nanobiotechnology. 2024 Apr 10;22(1):164. doi: 10.1186/s12951-024-02404-9.
Plasma proteins are considered the most informative source of biomarkers for disease diagnosis and monitoring. Mass spectrometry (MS)-based proteomics has been applied to identify biomarkers in plasma, but the complexity of the plasma proteome and the extremely large dynamic range of protein abundances in plasma make the clinical application of plasma proteomics highly challenging. We designed and synthesized zeolite-based nanoparticles to deplete high-abundance plasma proteins. The resulting novel plasma proteomic assay can measure approximately 3000 plasma proteins in a 45 min chromatographic gradient. Compared to those in neat and depleted plasma, the plasma proteins identified by our assay exhibited distinct biological profiles, as validated in several public datasets. A pilot investigation of the proteomic profile of a hepatocellular carcinoma (HCC) cohort identified 15 promising protein features, highlighting the diagnostic value of the plasma proteome in distinguishing individuals with and without HCC. Furthermore, this assay can be easily integrated with all current downstream protein profiling methods and potentially extended to other biofluids. In conclusion, we established a robust and efficient plasma proteomic assay with unprecedented identification depth, paving the way for the translation of plasma proteomics into clinical applications.
血浆蛋白被认为是疾病诊断和监测最有信息价值的生物标志物来源。基于质谱（MS）的蛋白质组学已被用于鉴定血浆中的生物标志物，但由于血浆蛋白质组的复杂性和蛋白质丰度的极大动态范围，使得血浆蛋白质组学的临床应用极具挑战性。我们设计并合成了基于沸石的纳米颗粒来耗尽高丰度的血浆蛋白。由此产生的新型血浆蛋白质组学分析方法可以在 45 分钟的色谱梯度内测量大约 3000 种血浆蛋白。与未经处理和耗尽处理的血浆相比，我们的分析方法所鉴定的血浆蛋白表现出明显不同的生物学特征，这在几个公共数据集的验证中得到了证实。对肝细胞癌（HCC）队列的蛋白质组学特征的初步研究确定了 15 个有前途的蛋白质特征，突出了血浆蛋白质组在区分 HCC 患者和非 HCC 患者方面的诊断价值。此外，该分析方法可以很容易地与所有当前的下游蛋白质分析方法集成，并可能扩展到其他生物流体。总之，我们建立了一种强大而高效的血浆蛋白质组学分析方法，具有前所未有的鉴定深度，为将血浆蛋白质组学转化为临床应用铺平了道路。
