Circulating exosomal microRNAs as biomarkers of colon cancer

Autor: Masatoshi Watanabe, Naoto Tsuchiya, Hitoshi Nakagama, Masashi Izumiya, Koh Furuta, Hiroko Ogata-Kawata, Hikaru Sonoda, Hiroyuki Okamoto, Takashi Kohno, Yoshitaka Honma, Toshiaki Gunji, Hideki Ohta, Jun Yokota, Yasuhide Yamada, Daisuke Kurioka
Rok vydání: 2013
Předmět:
Oncology
Male
Pathology
Microarray
Colorectal cancer
Epidemiology
lcsh:Medicine
Gene Expression
Exosomes
Pathology and Laboratory Medicine
Biochemistry
RNA interference
Nucleic Acids
Adenocarcinomas
Tumor Cells
Cultured
Medicine and Health Sciences
lcsh:Science
Multidisciplinary
Cancer Risk Factors
Colon Adenocarcinoma
Middle Aged
Gene Expression Regulation
Neoplastic
Colonic Neoplasms
Female
Epigenetics
HT29 Cells
Research Article
Adult
medicine.medical_specialty
Biology
Carcinomas
Breast cancer
Diagnostic Medicine
Internal medicine
Cell Line
Tumor
microRNA
Gastrointestinal Tumors
medicine
Biomarkers
Tumor
Genetics
Cancer Detection and Diagnosis
Humans
Aged
Biology and life sciences
Microarray analysis techniques
Gene Expression Profiling
lcsh:R
Cancer
Cancers and Neoplasms
medicine.disease
HCT116 Cells
Microarray Analysis
Microvesicles
digestive system diseases
Gene expression profiling
MicroRNAs
Biomarker Epidemiology
Case-Control Studies
RNA
lcsh:Q
Biomarkers
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 4, p e92921 (2014)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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