Integrative proteomic profiling of tumor and plasma extracellular vesicles identifies a diagnostic biomarker panel for colorectal cancer.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-04-30 DOI:10.1016/j.xcrm.2025.102090

Jun Wang, Chen-Zheng Gu, Peng-Xiang Wang, Jing-Rong Xian, Hao Wang, An-Quan Shang, Yu-Chen Zhong, Wen-Jing Zheng, Jian-Wen Cheng, Wen-Jing Yang, Jian Zhou, Jia Fan, Wei Guo, Xin-Rong Yang, Hao-Jie Lu

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引用次数: 0

Abstract

The lack of reliable non-invasive biomarkers for early colorectal cancer (CRC) diagnosis underscores the need for improved diagnostic tools. Extracellular vesicles (EVs) have emerged as promising candidates for liquid-biopsy-based cancer monitoring. Here, we propose a comprehensive workflow that integrates staged mass spectrometry (MS)-based discovery and verification with ELISA-based validation to identify EV protein biomarkers for CRC. Our approach, applied to 1,272 individuals, yields a machine learning model, ColonTrack, incorporating EV proteins HNRNPK, CTTN, and PSMC6. ColonTrack effectively distinguishes CRC from non-CRC cases and identifies early-stage CRC with high accuracy (combined area under the curve [AUC] >0.97, sensitivity ∼0.94, specificity ∼0.93). Our analysis of EV protein profiles from tissue and plasma demonstrates ColonTrack's potential as a robust non-invasive biomarker panel for CRC diagnosis and early detection.

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肿瘤和血浆细胞外囊泡的综合蛋白质组学分析确定了结直肠癌的诊断生物标志物面板。

早期结直肠癌（CRC）诊断缺乏可靠的非侵入性生物标志物，这强调了改进诊断工具的必要性。细胞外囊泡（EVs）已成为基于液体活检的癌症监测的有希望的候选者。在这里，我们提出了一个综合的工作流程，将基于阶段质谱（MS）的发现和验证与基于elisa的验证相结合，以鉴定结直肠癌的EV蛋白生物标志物。我们的方法应用于1,272个个体，产生了一个机器学习模型，ColonTrack，包含EV蛋白HNRNPK， CTTN和PSMC6。ColonTrack能有效区分结直肠癌和非结直肠癌，并能高精度地识别早期结直肠癌（合并曲线下面积[AUC] >0.97，灵敏度~ 0.94，特异性~ 0.93）。我们对组织和血浆中EV蛋白谱的分析表明，ColonTrack有潜力作为CRC诊断和早期检测的强大的非侵入性生物标志物面板。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.