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<p>Tumor-derived extracellular vesicles and particles (EVPs) represent a promising analyte class for early cancer detection. However, discrimination of tumor-derived EVPs from those shed by healthy tissues represents a major analytical challenge. This work describes the design and characterization of a novel proximity ligation-based immunoassay which targets tumor-derived EVPs in plasma displaying four colocalized surface biomarkers. We demonstrate the functionality of this approach in cancer cell line-derived EVPs and apply the method to lung adenocarcinoma (LUAD) detection. Importantly, we find that requiring four colocalized cancer-associated biomarkers reduces interference from healthy EVPs versus a three-biomarker design, resulting in strong discrimination performance for several biomarker combinations. Using this approach, we developed a prototype assay for LUAD detection which was evaluated in a case-control study composed of 92 LUAD cases and 290 non-cancer controls. The assay and trained classifier exhibited 48.5% (33/68; 95% confidence interval (CI) 37.1–60.2%) stage I sensitivity, 83.3% (15/18; 95% CI 59.8–94.8%) stage II sensitivity, and 100% (6/6; 95% CI 55.2–100%) stage III/IV sensitivity at 90% specificity. Assay signal was significantly correlated with tumor size and uncorrelated with smoking history. These preliminary results demonstrate the technical feasibility of this platform for early-stage lung cancer detection.</p>

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Detection of early-stage lung adenocarcinoma using a novel extracellular vesicle and particle-based blood test

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月11日

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  • Ibukunoluwapo O. Zabroski,
  • Daniel P. Salem,
  • Aaron Chevalier,
  • Timothy Santos-Heiman,
  • Nina A. Insixiengmay,
  • Brittany Grimes,
  • Katherine S. Yang,
  • Gabrielle N. Barcaskey,
  • MacKenzie S. King,
  • Syrena C. Fernandes,
  • Troy B. Hawkins,
  • Michael J. Smith,
  • Brendan J. Manning,
  • Dawn R. Mattoon,
  • Toumy Guettouche

摘要

Tumor-derived extracellular vesicles and particles (EVPs) represent a promising analyte class for early cancer detection. However, discrimination of tumor-derived EVPs from those shed by healthy tissues represents a major analytical challenge. This work describes the design and characterization of a novel proximity ligation-based immunoassay which targets tumor-derived EVPs in plasma displaying four colocalized surface biomarkers. We demonstrate the functionality of this approach in cancer cell line-derived EVPs and apply the method to lung adenocarcinoma (LUAD) detection. Importantly, we find that requiring four colocalized cancer-associated biomarkers reduces interference from healthy EVPs versus a three-biomarker design, resulting in strong discrimination performance for several biomarker combinations. Using this approach, we developed a prototype assay for LUAD detection which was evaluated in a case-control study composed of 92 LUAD cases and 290 non-cancer controls. The assay and trained classifier exhibited 48.5% (33/68; 95% confidence interval (CI) 37.1–60.2%) stage I sensitivity, 83.3% (15/18; 95% CI 59.8–94.8%) stage II sensitivity, and 100% (6/6; 95% CI 55.2–100%) stage III/IV sensitivity at 90% specificity. Assay signal was significantly correlated with tumor size and uncorrelated with smoking history. These preliminary results demonstrate the technical feasibility of this platform for early-stage lung cancer detection.