Issue 44, 2024

A simplified and efficient extracellular vesicle-based proteomics strategy for early diagnosis of colorectal cancer

Abstract

Colorectal cancer (CRC) is a major cause of cancer-related death worldwide and an effective screening strategy for diagnosis of early-stage CRC is highly desired. Although extracellular vesicles (EVs) are expected to become some of the most promising tools for liquid biopsy of early disease diagnosis, the existing EV-based proteomics methods for practical application in clinical samples are limited by technical challenges in high-throughput isolation and detection of EVs. In the current study, we have developed a simplified and efficient EV-based proteomics strategy for early diagnosis of CRC. DSPE-functionalized beads were specifically designed that enabled direct capture of EVs from plasma samples in 10 minutes with good reproducibility and comprehensive proteome coverage. The single-pot, solid-phase-enhanced sample-preparation (SP3) technology was then combined with data-independent acquisition mass spectrometry (DIA-MS) for in-depth analysis and quantification of EV proteomes. From a cohort with 30 individuals including 11 healthy controls, 8 patients with adenomatous polyp and 11 patients with early-stage CRC, our streamlined workflow reproducibly quantified over 800 proteins from their plasma-derived EV samples, from which dysregulated protein signatures for molecular diagnosis of CRC were revealed. We selected a panel of 10 protein markers to train a machine learning (ML) model, which resulted in accurate prediction of polyp and early-stage CRC in an independent and single-blind validation cohort with excellent diagnostic ability of 89.3% accuracy. Our simplified and efficient clinical proteomic strategy will serve as a valuable tool for fast, accurate, and cost-effective diagnosis of CRC that can be easily extended to other disease samples for discovery of unique EV-based biomarkers.

Graphical abstract: A simplified and efficient extracellular vesicle-based proteomics strategy for early diagnosis of colorectal cancer

Supplementary files

Article information

Article type
Edge Article
Submitted
16 Aug 2024
Accepted
08 Oct 2024
First published
15 Oct 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2024,15, 18419-18430

A simplified and efficient extracellular vesicle-based proteomics strategy for early diagnosis of colorectal cancer

J. Zhang, Z. Gao, W. Xiao, N. Jin, J. Zeng, F. Wang, X. Jin, L. Dong, J. Lin, J. Gu and C. Wang, Chem. Sci., 2024, 15, 18419 DOI: 10.1039/D4SC05518G

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements