Machine learning-based analysis identifies and validates serum exosomal proteomic signatures for the diagnosis of colorectal cancer.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2024-08-20 DOI:10.1016/j.xcrm.2024.101689

Haofan Yin, Jinye Xie, Shan Xing, Xiaofang Lu, Yu Yu, Yong Ren, Jian Tao, Guirong He, Lijun Zhang, Xiaopeng Yuan, Zheng Yang, Zhijian Huang

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Abstract

The potential of serum extracellular vesicles (EVs) as non-invasive biomarkers for diagnosing colorectal cancer (CRC) remains elusive. We employed an in-depth 4D-DIA proteomics and machine learning (ML) pipeline to identify key proteins, PF4 and AACT, for CRC diagnosis in serum EV samples from a discovery cohort of 37 cases. PF4 and AACT outperform traditional biomarkers, CEA and CA19-9, detected by ELISA in 912 individuals. Furthermore, we developed an EV-related random forest (RF) model with the highest diagnostic efficiency, achieving AUC values of 0.960 and 0.963 in the train and test sets, respectively. Notably, this model demonstrated reliable diagnostic performance for early-stage CRC and distinguishing CRC from benign colorectal diseases. Additionally, multi-omics approaches were employed to predict the functions and potential sources of serum EV-derived proteins. Collectively, our study identified the crucial proteomic signatures in serum EVs and established a promising EV-related RF model for CRC diagnosis in the clinic.

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基于机器学习的分析确定并验证了用于诊断结直肠癌的血清外泌体蛋白质组特征。

血清细胞外囊泡（EVs）作为诊断结直肠癌（CRC）的非侵入性生物标记物的潜力仍然难以捉摸。我们采用了深入的4D-DIA蛋白质组学和机器学习（ML）管道，从37个病例的发现队列的血清EV样本中鉴定出了用于诊断CRC的关键蛋白质PF4和AACT。在912例患者中，PF4和AACT的表现优于ELISA检测的传统生物标记物CEA和CA19-9。此外，我们还开发了一种与 EV 相关的随机森林（RF）模型，其诊断效率最高，在训练集和测试集中的 AUC 值分别达到了 0.960 和 0.963。值得注意的是，该模型对早期 CRC 和区分 CRC 与良性结直肠疾病具有可靠的诊断性能。此外，我们还采用了多组学方法来预测血清 EV 衍生蛋白的功能和潜在来源。总之，我们的研究确定了血清 EV 中关键的蛋白质组特征，并为临床诊断 CRC 建立了一个前景良好的 EV 相关 RF 模型。

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.