Enhanced Early Detection of Colorectal Cancer via Blood Biomarker Combinations Identified Through Extracellular Vesicle Isolation and Artificial Intelligence Analysis

ABSTRACT Colorectal cancer (CRC) remains a major cause of cancer‐related deaths worldwide, with early detection being crucial for improving survival rates. Despite the potential of extracellular vesicles (EVs) as blood biomarkers for CRC diagnosis, their clinical utility is limited due to complex an...

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Main Authors: Bonhan Koo, Young Il Kim, Minju Lee, Seok‐Byung Lim, Yong Shin
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Journal of Extracellular Vesicles
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Online Access:https://doi.org/10.1002/jev2.70088
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author Bonhan Koo
Young Il Kim
Minju Lee
Seok‐Byung Lim
Yong Shin
author_facet Bonhan Koo
Young Il Kim
Minju Lee
Seok‐Byung Lim
Yong Shin
author_sort Bonhan Koo
collection DOAJ
description ABSTRACT Colorectal cancer (CRC) remains a major cause of cancer‐related deaths worldwide, with early detection being crucial for improving survival rates. Despite the potential of extracellular vesicles (EVs) as blood biomarkers for CRC diagnosis, their clinical utility is limited due to complex and time‐consuming isolation methods, unverified biomarkers and low diagnostic performance. Here, we introduce the ZAHV‐AI system, which combines the zeolite‐amine and homobifunctional hydrazide‐based extracellular vesicle isolation (ZAHVIS) platform with AI‐driven analysis for enhanced CRC diagnosis. The ZAHVIS platform enables simple, rapid and cost‐effective EV isolation and one‐step extraction of EV‐derived proteins and nucleic acids (NAs), providing a streamlined approach. Using blood plasma samples from 80 CRC patients across all stages and 20 healthy individuals, we identified four EV‐derived miRNA blood biomarkers (miR‐23a‐3p, miR‐92a‐3p, miR‐125a‐3p and miR‐150‐5p) by confirming statistical significance with relative quantification (RQ) values from real‐time PCR and integrated these with carcinoembryonic antigen (CEA) levels into an AI‐driven diagnostic model. Among 31 combinations used to identify optimal sets, optimal combination (miR‐23a‐3p, miR‐92a‐3p, miR‐150‐5p and CEA) for overall CRC achieved an area under the curve (AUC) of 0.9861, outperforming individual markers and conventional CEA tests. Notably, the system achieved perfect performance in detecting stages 0–1 (AUC: 1.0) and demonstrated high accuracy for stage 2 (AUC: 0.9722) and early‐stage CRC (AUC: 0.9861), using stage‐specific optimal combinations. Therefore, the ZAHV‐AI system offers a reliable and clinically relevant tool for CRC diagnostics, significantly enhancing early detection and monitoring capabilities.
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spelling doaj-art-e64975fc037e40118adeda0f185ada262025-08-20T02:48:54ZengWileyJournal of Extracellular Vesicles2001-30782025-06-01146n/an/a10.1002/jev2.70088Enhanced Early Detection of Colorectal Cancer via Blood Biomarker Combinations Identified Through Extracellular Vesicle Isolation and Artificial Intelligence AnalysisBonhan Koo0Young Il Kim1Minju Lee2Seok‐Byung Lim3Yong Shin4Department of Biotechnology, College of Life Science and Biotechnology Yonsei University Seodaemun‐gu Republic of KoreaDivision of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center University of Ulsan College of Medicine Songpa‐gu Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology Yonsei University Seodaemun‐gu Republic of KoreaDivision of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center University of Ulsan College of Medicine Songpa‐gu Republic of KoreaDepartment of Biotechnology, College of Life Science and Biotechnology Yonsei University Seodaemun‐gu Republic of KoreaABSTRACT Colorectal cancer (CRC) remains a major cause of cancer‐related deaths worldwide, with early detection being crucial for improving survival rates. Despite the potential of extracellular vesicles (EVs) as blood biomarkers for CRC diagnosis, their clinical utility is limited due to complex and time‐consuming isolation methods, unverified biomarkers and low diagnostic performance. Here, we introduce the ZAHV‐AI system, which combines the zeolite‐amine and homobifunctional hydrazide‐based extracellular vesicle isolation (ZAHVIS) platform with AI‐driven analysis for enhanced CRC diagnosis. The ZAHVIS platform enables simple, rapid and cost‐effective EV isolation and one‐step extraction of EV‐derived proteins and nucleic acids (NAs), providing a streamlined approach. Using blood plasma samples from 80 CRC patients across all stages and 20 healthy individuals, we identified four EV‐derived miRNA blood biomarkers (miR‐23a‐3p, miR‐92a‐3p, miR‐125a‐3p and miR‐150‐5p) by confirming statistical significance with relative quantification (RQ) values from real‐time PCR and integrated these with carcinoembryonic antigen (CEA) levels into an AI‐driven diagnostic model. Among 31 combinations used to identify optimal sets, optimal combination (miR‐23a‐3p, miR‐92a‐3p, miR‐150‐5p and CEA) for overall CRC achieved an area under the curve (AUC) of 0.9861, outperforming individual markers and conventional CEA tests. Notably, the system achieved perfect performance in detecting stages 0–1 (AUC: 1.0) and demonstrated high accuracy for stage 2 (AUC: 0.9722) and early‐stage CRC (AUC: 0.9861), using stage‐specific optimal combinations. Therefore, the ZAHV‐AI system offers a reliable and clinically relevant tool for CRC diagnostics, significantly enhancing early detection and monitoring capabilities.https://doi.org/10.1002/jev2.70088artificial intelligence analysisbiomarker combinationsblood biomarkersearly diagnosticsextracellular vesicle isolation
spellingShingle Bonhan Koo
Young Il Kim
Minju Lee
Seok‐Byung Lim
Yong Shin
Enhanced Early Detection of Colorectal Cancer via Blood Biomarker Combinations Identified Through Extracellular Vesicle Isolation and Artificial Intelligence Analysis
Journal of Extracellular Vesicles
artificial intelligence analysis
biomarker combinations
blood biomarkers
early diagnostics
extracellular vesicle isolation
title Enhanced Early Detection of Colorectal Cancer via Blood Biomarker Combinations Identified Through Extracellular Vesicle Isolation and Artificial Intelligence Analysis
title_full Enhanced Early Detection of Colorectal Cancer via Blood Biomarker Combinations Identified Through Extracellular Vesicle Isolation and Artificial Intelligence Analysis
title_fullStr Enhanced Early Detection of Colorectal Cancer via Blood Biomarker Combinations Identified Through Extracellular Vesicle Isolation and Artificial Intelligence Analysis
title_full_unstemmed Enhanced Early Detection of Colorectal Cancer via Blood Biomarker Combinations Identified Through Extracellular Vesicle Isolation and Artificial Intelligence Analysis
title_short Enhanced Early Detection of Colorectal Cancer via Blood Biomarker Combinations Identified Through Extracellular Vesicle Isolation and Artificial Intelligence Analysis
title_sort enhanced early detection of colorectal cancer via blood biomarker combinations identified through extracellular vesicle isolation and artificial intelligence analysis
topic artificial intelligence analysis
biomarker combinations
blood biomarkers
early diagnostics
extracellular vesicle isolation
url https://doi.org/10.1002/jev2.70088
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