Circulating Exosomal microRNAs as Biomarkers of Colon Cancer
By Hiroko Ogata-Kawata, M. Izumiya, Daisuke Kurioka, Y. Honma, Y. Yamada, K. Furuta, T. Gunji, Hideki Ohta, Hiroyuki Okamoto, H. Sonoda and 5 more. PLoS ONE, 2014
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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.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f90c628bba9c9b9e8a56fe40ee066f3f771946b6
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Citations in the corpus
- Extracellular vesicles in cancer: cell-to-cell mediators of metastasis (2016, background): “These miRNA levels decreased after surgical resection of tumor, suggesting their potential tumor origin (Ogata-Kawata et al., 2014).”
- Precision Cancer Medicine: Challenges and Opportunities (2019, background): “Gene panels may also exhibit increased sensitivity for detecting clinically actionable alterations compared to WES and WGS, owing to deeper sequence coverage in these most important genomic regions [121].”
- WBSMDA: Within and Between Score for MiRNA-Disease Association prediction (2016, background): “Colon Neoplasms (CN) are a big threaten to people’s lives with a low detection rate at early stages 54,55 .”
- Exosome and Exosomal MicroRNA: Trafficking, Sorting, and Function (2015, background): “…from normal tissue and tumors [29,41,52,55,56]. miR-150 is highly expressed in exosomes derived from the HEK293T cell line, peripheral blood of tumor patients, colony-stimulating factor 1 (CSF-1)-induced bone marrow-derived macrophages, and the serum of colon cancer patients [52,54,55,57,58].”
- Brief update on endocytosis of nanomedicines (2019, background): “Exosomes isolated from patients with cancers contain specific biomarkers, highlighting their potential in cancer diagnostics and early detection [173,174].”