Issue 6, 2023

Plasma extracellular vesicle phenotyping for the differentiation of early-stage lung cancer and benign lung diseases

Abstract

The development of a minimally invasive technique for early-stage lung cancer detection is crucial to reducing mortality. Phenotyping of tumor-associated extracellular vesicles (EVs) has the potential for early-stage lung cancer detection, yet remains challenging due to the lack of sensitive, integrated techniques that can accurately detect rare tumor-associated EV populations in blood. Here, we integrated gold core–silver shell nanoparticles and nanoscopic mixing in a microfluidic assay for sensitive phenotypic analysis of EVs directly in plasma without EV pre-isolation. The assay enabled multiplex detection of lung cancer-associated markers PTX3 and THBS1 and canonical EV marker CD63 by surface-enhanced Raman spectroscopy, providing a squared correlation coefficient of 0.97 in the range of 103–107 EVs mL−1 and a limit of detection of 19 EVs mL−1. Significantly, our machine learning-based nanostrategy provided 92.3% sensitivity and 100% specificity in differentiating early-stage lung cancer from benign lung diseases, superior to the CT scan-based lung cancer diagnosis (92.3% sensitivity and 71.4% specificity). Overall, our integrated nanostrategy achieved an AUC value of 0.978 in differentiating between early-stage lung cancer patients (n = 28) and controls consisting of patients with benign lung diseases (n = 23) and healthy controls (n = 26), which showed remarkable diagnostic performance and great clinical potential for detecting the early occurrence of lung cancer.

Graphical abstract: Plasma extracellular vesicle phenotyping for the differentiation of early-stage lung cancer and benign lung diseases

Associated articles

Supplementary files

Article information

Article type
Communication
Submitted
07 Dec 2022
Accepted
15 Mar 2023
First published
16 Mar 2023

Nanoscale Horiz., 2023,8, 746-758

Plasma extracellular vesicle phenotyping for the differentiation of early-stage lung cancer and benign lung diseases

L. Yuan, Y. Chen, L. Ke, Q. Zhou, J. Chen, M. Fan, A. Wuethrich, M. Trau and J. Wang, Nanoscale Horiz., 2023, 8, 746 DOI: 10.1039/D2NH00570K

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