4.7 Article

Clinical impact of serum exosomal microRNA-21 as a clinical biomarker in human esophageal squamous cell carcinoma

Journal

CANCER
Volume 119, Issue 6, Pages 1159-1167

Publisher

WILEY-BLACKWELL
DOI: 10.1002/cncr.27895

Keywords

exosome; microRNA; human microRNA-21; esophageal cancer

Categories

Funding

  1. Japan Society for the Promotion of Science [23791550]
  2. Takeda Science Foundation
  3. Okukubo Memorial Fund for Medical Research in Kumamoto University School of Medicine
  4. Uehara Memorial Foundation
  5. Yokoyama Foundation for Clinical Pharmacology
  6. Grants-in-Aid for Scientific Research [23591940, 22390247, 23791550] Funding Source: KAKEN

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BACKGROUND: Exosomes are 40-nm to 100-nm membrane vesicles that are secreted by various cells, and they play a major role in cell-cell communication. The objective of this study was to clarify the significance of the levels of microRNA in exosomes extracted from the sera of patients with esophageal squamous cell cancer (ESCC). METHODS: The authors isolated exosomes in serum samples from patients who had ESCC and from patients who had benign diseases without systemic inflammation. Total RNA was purified from the exosomes, and expression levels of microRNA-21 (miR-21) were analyzed by quantitative real-time polymerase chain reaction. RESULTS: Serum exosomes from patients with ESCC induced the proliferation of ESCC cells in vitro. The expression levels of exosomal miR-21 were significantly higher in patients with ESCC than those with benign diseases with and without (C-reactive protein <0.3 mg/dL) systemic inflammation. MiR-21 was not detected in serum that remained after exosome extraction. Exosomal miR-21 expression was correlated with advanced tumor classification, positive lymph node status, and the presence of metastasis with inflammation or and clinical stage without inflammation (C-reactive protein <0.3 mg/dL). CONCLUSIONS: The current results confirmed that exosomal miR-21 expression is up-regulated in serum from patients with ESCC versus serum from patients who have benign diseases without systemic inflammation. Exosomal miR-21 was positively correlated with tumor progression and aggressiveness, suggesting that it may be a useful target for cancer therapy. Cancer 2013. (c) 2012 American Cancer Society.

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