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适配体偶联多晶碳上的外泌体代谢模式用于早期胃癌的精准检测

Exosome Metabolic Patterns on Aptamer-Coupled Polymorphic Carbon for Precise Detection of Early Gastric Cancer.

作者信息

Chen Haolin, Huang Chuwen, Wu Yonglei, Sun Nianrong, Deng Chunhui

机构信息

Department of Chemistry, Metabolism and Integrative Biology (IMIB), Zhongshan Hospital, Fudan University, Shanghai 200433, China.

Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

出版信息

ACS Nano. 2022 Aug 23;16(8):12952-12963. doi: 10.1021/acsnano.2c05355. Epub 2022 Aug 10.

Abstract

Gastric cancer (GC) presents high mortality worldwide because of delayed diagnosis. Currently, exosome-based liquid biopsy has been applied in diagnosis and monitoring of diseases including cancers, whereas disease detection based on exosomes at the metabolic level is rarely reported. Herein, the specific aptamer-coupled Au-decorated polymorphic carbon (CoMPC@Au-Apt) is constructed for the capture of urinary exosomes from early GC patients and healthy controls (HCs) and the subsequent exosome metabolic pattern profiling without extra elution process. Combining with machine learning algorithm on all exosome metabolic patterns, the early GC patients are excellently discriminated from HCs, with an accuracy of 100% for both the discovery set and blind test. Ulteriorly, three key metabolic features with clear identities are determined as a biomarker panel, obtaining a more than 90% diagnostic accuracy for early GC in the discovery set and validation set. Moreover, the change law of the key metabolic features along with GC development is revealed through making a comparison among HCs and GC at early stage and advanced stage, manifesting their monitoring ability toward GC. This work illustrates the high specificity of exosomes and the great prospective of exosome metabolic analysis in disease diagnosis and monitoring, which will promote exosome-driven precision medicine toward practical clinical application.

摘要

由于诊断延迟,胃癌(GC)在全球范围内具有较高的死亡率。目前,基于外泌体的液体活检已应用于包括癌症在内的疾病的诊断和监测,而基于外泌体在代谢水平上的疾病检测鲜有报道。在此,构建了特异性适配体偶联金修饰的多晶碳(CoMPC@Au-Apt),用于从早期胃癌患者和健康对照(HCs)中捕获尿液外泌体,并在无需额外洗脱过程的情况下对后续外泌体代谢模式进行分析。结合机器学习算法对所有外泌体代谢模式进行分析,早期胃癌患者与健康对照能够得到很好的区分,发现集和盲测的准确率均为100%。进一步地,确定了具有明确特征的三个关键代谢特征作为生物标志物组合,在发现集和验证集中对早期胃癌的诊断准确率均超过90%。此外,通过比较健康对照、早期胃癌和晚期胃癌,揭示了关键代谢特征随胃癌发展的变化规律,表明了它们对胃癌的监测能力。这项工作说明了外泌体的高特异性以及外泌体代谢分析在疾病诊断和监测中的巨大前景,这将推动以外泌体为驱动的精准医学走向实际临床应用。

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