Cited by 810Extracellular vesicles in diseaseMicroRNA in disease regulationCancer-related molecular mechanisms research

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Circulating Exosomal microRNAs as Biomarkers of Colon Cancer

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Ogata-Kawata, Hiroko, Izumiya, Masashi, Kurioka, Daisuke, Honma, Yoshitaka, Yamada, Yasuhide, Furuta, Koh, Gunji, Toshiaki, Ohta, Hideki, Okamoto, Hiroyuki, Sonoda, Hikaru, Watanabe, Masatoshi, Nakagama, Hitoshi, Yokota, Jun, Kohno, Takashi, Tsuchiya, Naoto·2014·PLoS ONE

DOI 10.1371/journal.pone.0092921PMC PMC3976275

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Abstract

PURPOSE: Exosomal microRNAs (miRNAs) have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC). To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined. EXPERIMENTAL DESIGN: Microarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA) using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients. RESULTS: The serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a) were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis. CONCLUSION: Exosomal miRNA signatures appear to mirror pathological changes of CRC patients and several miRNAs are promising biomarkers for non-invasive diagnosis of the disease.

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Background
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Authors: Ogata-Kawata, H., Izumiya, M., Kurioka, D., Honma, Y., Yamada, Y., Furuta, K., Gunji, T., Ohta, H., Okamoto, H., Sonoda, H., Watanabe, M., Nakagama, H., Yokota, J., Kohno, T., & Tsuchiya, N.
Affiliations: University of Tokyo Hospital (JP)
Yokohama National University (JP)
National Cancer Center Hospital (JP)
NTT Medical Center (JP)
Shionogi (Japan) (JP)
National Cancer Center Research Institute (JP)
Institute of Predictive and Personalized Medicine of Cancer (ES)
Corresponding author: Tsuchiya, Naoto
ORCID: Izumiya, Masashi
Honma, Yoshitaka
Yamada, Yasuhide
Furuta, Koh
Gunji, Toshiaki
Sonoda, Hikaru
Watanabe, Masatoshi
Yokota, Jun
Kohno, Takashi
Tsuchiya, Naoto
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2014-04-04
Volume: 9
Issue: 4
Pages: e92921
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0092921
PMC: PMC3976275
OpenAlex: W1992970284
Cited by: 809
References: 37
Citations by year: 2026: 28 · 2025: 37 · 2024: 51 · 2023: 45 · 2022: 76 · 2021: 96 · 2020: 89 · 2019: 81 · 2018: 76 · 2017: 76 · 2016: 78 · 2015: 60 · 2014: 15
FWCI: 31.32
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Figshare (submittedVersion, cc-by)
Funders: National Institute of Biomedical Innovation
Japan Society for the Promotion of Science (23300359, 24790683)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords: exosomal microRNAs, colorectal cancer, serum exosomes, diagnostic biomarkers, non-invasive diagnosis, miR-21, miR-223, miR-23a, miR-150, miR-1246, let-7a, tumor resection, CA19-9, carcinoembryonic antigen
MeSH terms: Adult, Aged, Colonic Neoplasms, Female, Humans, Male, Middle Aged, Tumor Cells, Cultured, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Case-Control Studies, HT29 Cells, Gene Expression Profiling, MicroRNAs, HCT116 Cells, Cell Line, Tumor, Microarray Analysis, Exosomes

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Circulating Exosomal microRNAs as Biomarkers of Colon Cancer

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