Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality, largely due to late-stage diagnosis. Reliable early detection methods are critically needed. PDAC-derived extracellular vesicles (EVs) carry molecules that reflect their parental tumor cells and are detectable in early disease stages, offering a promising noninvasive diagnostic approach. Here, a streamlined PDAC EV Surface Protein Assay for quantifying PDAC EV subpopulations in 300-µL plasma through a two-step workflow is presented: i) click chemistry-mediated EV enrichment using EV Click Beads and trans-cyclooctene-grafted antibodies targeting three PDAC EV-specific surface proteins (MUC1, EGFR, and TROP2), and ii) quantification of enriched PDAC EVs through reverse transcription-quantitative polymerase chain reaction. The three PDAC EV-specific surface proteins are identified using a bioinformatics framework and validated on PDAC cell lines and tissue microarrays. The resultant PDAC EV Score, derived from signals of the three PDAC EV subpopulations, demonstrates robust differentiation of PDAC patients from noncancer controls, with area under the receiver operating characteristic curves of 0.94 in the training (n = 124) and 0.93 in the validation (n = 136) cohorts. This EV-based diagnostic approach successfully exploits PDAC EV subpopulations as novel biomarkers for PDAC early detection, translating PDAC surface proteins into an EV-based liquid biopsy platform.

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Publication Details

Journal
Advanced Science
Published
2025-03-25
DOI
https://doi.org/10.1002/advs.202414982
Citations
12
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
9.67

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article

Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma

Zhenfang Wang, An Min Wang, Hyo Yong Kim, Hui Kong et al.
12 citations
Advanced Science
Extracellular vesicles in disease
9.67
article

Identification of Tumor‐Specific Surface Proteins Enables Quantification of Extracellular Vesicle Subtypes for Early Detection of Pancreatic Ductal Adenocarcinoma

Zhenfang Wang, An Min Wang, Hyo Yong Kim, Hui Kong, Jipeng Wan, Myung‐Shin Sim, Yazhen Zhu, Stephen J. Pandol, Sungyong You, Ryan Y. Zhang, Hsian‐Rong Tseng, Jianwei Yang, Jina Kim, Dejun Liu, Yong Ju, Yating Zhang, Junseok Lee, Shaohua Lu, Shujing Guo, Na Sun, Bing Cheng Feng, Zhili Wang, Chen Zhao, James S. Tomlinson, Renjun Pei, Ding Ma, Dekang Gao, Yandong Zhang
article en
12 citations

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality, largely due to late-stage diagnosis. Reliable early detection methods are critically needed. PDAC-derived extracellular vesicles (EVs) carry molecules that reflect their parental tumor cells and are detectable in early disease stages, offering a promising noninvasive diagnostic approach. Here, a streamlined PDAC EV Surface Protein Assay for quantifying PDAC EV subpopulations in 300-µL plasma through a two-step workflow is presented: i) click chemistry-mediated EV enrichment using EV Click Beads and trans-cyclooctene-grafted antibodies targeting three PDAC EV-specific surface proteins (MUC1, EGFR, and TROP2), and ii) quantification of enriched PDAC EVs through reverse transcription-quantitative polymerase chain reaction. The three PDAC EV-specific surface proteins are identified using a bioinformatics framework and validated on PDAC cell lines and tissue microarrays. The resultant PDAC EV Score, derived from signals of the three PDAC EV subpopulations, demonstrates robust differentiation of PDAC patients from noncancer controls, with area under the receiver operating characteristic curves of 0.94 in the training (n = 124) and 0.93 in the validation (n = 136) cohorts. This EV-based diagnostic approach successfully exploits PDAC EV subpopulations as novel biomarkers for PDAC early detection, translating PDAC surface proteins into an EV-based liquid biopsy platform.

Advanced ScienceVol. 12(21)
University of Science and Technology of China (CN), Cedars-Sinai Medical Center (US), California NanoSystems Institute (US), Sun Yat-sen University (CN), University of California, Los Angeles (US), Chinese Academy of Sciences (CN), Fudan University (CN), Renji Hospital (CN), Wuhan University (CN), Soochow University (CN), Suzhou Institute of Nano-tech and Nano-bionics (CN), Nanfang Hospital (CN), Second Affiliated Hospital of Soochow University (CN), Zhongshan Hospital (CN), The First Affiliated Hospital, Sun Yat-sen University (CN), Renmin Hospital of Wuhan University (CN), Southern Medical University (CN)
Natural Science Foundation of Hubei Province, Youth Innovation Promotion Association of the Chinese Academy of Sciences, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 2%
Extracellular vesicles in disease
9.67
DOIOpen Access PDFOpenAlex
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