Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 Apr 4;9(4):e92921. doi: 10.1371/journal.pone.0092921. eCollection 2014.

Circulating exosomal microRNAs as biomarkers of colon cancer.

Author information

1
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
2
Department of Gastroenterology, The University of Tokyo Hospital, Tokyo, Japan.
3
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan; Laboratory for Medical Engineering, Division of Materials and Chemical Engineering, Graduate School of Engineering, Yokohama National University, Kanagawa, Japan.
4
Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
5
Division of Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
6
NTT Medical Center Tokyo, Tokyo, Japan.
7
Shionogi & Co., Ltd., Osaka, Japan.
8
Laboratory for Medical Engineering, Division of Materials and Chemical Engineering, Graduate School of Engineering, Yokohama National University, Kanagawa, Japan.
9
Division of Cancer Development System, National Cancer Center Research Institute, Tokyo, Japan.
10
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan; Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain.

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.

PMID:
24705249
PMCID:
PMC3976275
DOI:
10.1371/journal.pone.0092921
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center