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Multiplexed analysis of EV reveals specific biomarker composition with diagnostic impact

Author

Listed:
  • Joshua D. Spitzberg

    (Massachusetts General Hospital)

  • Scott Ferguson

    (Massachusetts General Hospital)

  • Katherine S. Yang

    (Massachusetts General Hospital)

  • Hannah M. Peterson

    (Massachusetts General Hospital)

  • Jonathan C. T. Carlson

    (Massachusetts General Hospital
    Cancer Center, Massachusetts General Hospital)

  • Ralph Weissleder

    (Massachusetts General Hospital
    Cancer Center, Massachusetts General Hospital
    Harvard Medical School)

Abstract

Exosomes and extracellular vesicles (EV) are increasingly being explored as circulating biomarkers, but their heterogenous composition will likely mandate the development of multiplexed EV technologies. Iteratively multiplexed analyses of near single EVs have been challenging to implement beyond a few colors during spectral sensing. Here we developed a multiplexed analysis of EV technique (MASEV) to interrogate thousands of individual EVs during 5 cycles of multi-channel fluorescence staining for 15 EV biomarkers. Contrary to the common belief, we show that: several markers proposed to be ubiquitous are less prevalent than believed; multiple biomarkers concur in single vesicles but only in small fractions; affinity purification can lead to loss of rare EV subtypes; and deep profiling allows detailed analysis of EV, potentially improving the diagnostic content. These findings establish the potential of MASEV for uncovering fundamental EV biology and heterogeneity and increasing diagnostic specificity.

Suggested Citation

  • Joshua D. Spitzberg & Scott Ferguson & Katherine S. Yang & Hannah M. Peterson & Jonathan C. T. Carlson & Ralph Weissleder, 2023. "Multiplexed analysis of EV reveals specific biomarker composition with diagnostic impact," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36932-z
    DOI: 10.1038/s41467-023-36932-z
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    1. Fredrik Edfors & Andreas Hober & Klas Linderbäck & Gianluca Maddalo & Alireza Azimi & Åsa Sivertsson & Hanna Tegel & Sophia Hober & Cristina Al-Khalili Szigyarto & Linn Fagerberg & Kalle Feilitzen & P, 2018. "Enhanced validation of antibodies for research applications," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
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    3. Sonia A. Melo & Linda B. Luecke & Christoph Kahlert & Agustin F. Fernandez & Seth T. Gammon & Judith Kaye & Valerie S. LeBleu & Elizabeth A. Mittendorf & Juergen Weitz & Nuh Rahbari & Christoph Reissf, 2015. "Glypican-1 identifies cancer exosomes and detects early pancreatic cancer," Nature, Nature, vol. 523(7559), pages 177-182, July.
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    1. Alexia Stollmann & Jose Garcia-Guirado & Jae-Sang Hong & Pascal Rüedi & Hyungsoon Im & Hakho Lee & Jaime Ortega Arroyo & Romain Quidant, 2024. "Molecular fingerprinting of biological nanoparticles with a label-free optofluidic platform," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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