Hamza Ghaith M, Raghunathan Rekha, Ashenden Stephanie, Zhang Bairu, Miele Eric, Jarnuczak Andrew F
Discovery Sciences, R&D, AstraZeneca, Cambridge, UK.
Bioanalytical and Biomarker, Prevail Therapeutics, Wholly Owned Subsidiary of Eli Lilly and Company, New York, NY, 10016, USA.
Clin Proteomics. 2024 Mar 12;21(1):21. doi: 10.1186/s12014-024-09461-0.
Despite progress, MS-based proteomics in biofluids, especially blood, faces challenges such as dynamic range and throughput limitations in biomarker and disease studies. In this work, we used cutting-edge proteomics technologies to construct label-based and label-free workflows, capable of quantifying approximately 2,000 proteins in biofluids. With 70µL of blood and a single depletion strategy, we conducted an analysis of a homogenous cohort (n = 32), comparing medium-grade prostate cancer patients (Gleason score: 7(3 + 4); TNM stage: T2cN0M0, stage IIB) to healthy donors. The results revealed dozens of differentially expressed proteins in both plasma and serum. We identified the upregulation of Prostate Specific Antigen (PSA), a well-known biomarker for prostate cancer, in the serum of cancer cohort. Further bioinformatics analysis highlighted noteworthy proteins which appear to be differentially secreted into the bloodstream, making them good candidates for further exploration.
尽管取得了进展，但基于质谱的生物流体蛋白质组学，尤其是血液蛋白质组学，在生物标志物和疾病研究中仍面临诸如动态范围和通量限制等挑战。在这项工作中，我们使用了前沿蛋白质组学技术构建基于标签和无标签的工作流程，能够对生物流体中约2000种蛋白质进行定量分析。我们用70微升血液和单一的去除策略，对一个同质队列（n = 32）进行了分析，将中度前列腺癌患者（ Gleason评分：7(3 + 4)；TNM分期：T2cN0M0，IIB期）与健康供体进行比较。结果显示，血浆和血清中都有数十种差异表达的蛋白质。我们在癌症队列的血清中发现了前列腺特异性抗原（PSA）的上调，PSA是一种众所周知的前列腺癌生物标志物。进一步的生物信息学分析突出了一些值得注意的蛋白质，这些蛋白质似乎差异分泌到血液中，使其成为进一步探索的良好候选对象。
