Efficient Cancer Biomarker Screening and Multicancer Detection Enabled by a Multidimensional Serum Proteomic Strategy

IF 6.7 1区化学 Q1 CHEMISTRY, ANALYTICAL Analytical Chemistry Pub Date : 2024-11-21 DOI:10.1021/acs.analchem.4c03006

Anqi Hu, Jiayi Zhang, Lei Zhang, Zhenxin Wang, Jiawei Dai, Ling Lin, Guoquan Yan, Fenglin Shen, Huali Shen

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Abstract

Biomarker discovery and application are paramount for the early diagnosis, treatment, and prognosis assessment of diseases. Novel proteomic strategies have been developed for high-efficiency biomarker screening. However, evaluating various strategies and applying them for the in-depth mining of biomarkers from blood need to be elucidated. Herein, we systematically evaluated the technical characteristics of three representative biomarker discovery strategies, including the most popular DIA proteomics, and two promising strategies targeting the cancer-secreted proteome or extracellular vesicle proteome, and integrated them into one multidimensional serum proteomic strategy. The results showed that the three strategies each have unique characteristics in terms of sensitivity, reproducibility, and protein coverage and are highly complementary in biomarker discovery. The integrated multidimensional serum proteomic strategy achieves deep and comprehensive coverage of the serum proteome, discovers more cancer markers, and helps achieve a more accurate multicancer (breast, lung, stomach, liver, and colorectum) diagnosis with 87.5% localization accuracy.

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通过多维血清蛋白质组策略实现高效的癌症生物标记物筛查和多发性癌症检测

生物标志物的发现和应用对于疾病的早期诊断、治疗和预后评估至关重要。为高效筛选生物标志物，人们开发了新的蛋白质组学策略。然而，评估各种策略并将其应用于深入挖掘血液中的生物标记物还有待进一步阐明。在本文中，我们系统评估了三种代表性生物标志物发现策略的技术特点，包括最流行的DIA蛋白质组学，以及两种针对癌症分泌蛋白质组或细胞外囊泡蛋白质组的有前途的策略，并将它们整合为一种多维血清蛋白质组学策略。结果表明，这三种策略在灵敏度、重现性和蛋白质覆盖率方面各有特点，在生物标记物发现方面具有很强的互补性。整合后的多维血清蛋白质组策略实现了对血清蛋白质组的深度和全面覆盖，发现了更多癌症标志物，有助于实现更准确的多癌症（乳腺癌、肺癌、胃癌、肝癌和结直肠癌）诊断，定位准确率达87.5%。

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来源期刊

Analytical Chemistry 化学-分析化学

CiteScore

12.10

自引率

12.20%

发文量

1949

审稿时长

1.4 months

期刊介绍： Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.

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