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

Abstract

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.

The biology and function of exosomes in cancer

“…Unique nucleic acids (mutant mRNA such as the epidermal growth factor receptor EGFRvIII variant) contained in exosomes could potentially serve as reliable biomarkers for glioblastoma (43). Enriched and specific miRs in exosomes may also inform diagnosis and serve to monitor the progression of cancer (16,(44)(45)(46)(47)(48). For example, exosomal miR-21 is increased in the serum of patients with esophageal squamous cell carcinoma and correlates with advanced disease stage (45).…”

Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer

“…However, the existing biomarkers, such as cancer-associated antigens, and proteomics analysis are unsatisfactory for the early stages of NSCLC. By contrast, recent studies have demonstrated that specific expression profiles of circulating exosomal miRNAs could be promising biomarkers for the detection of early-stage cancer and for predicting prognosis in various types of cancers (19)(20)(21). However, previous studies in NSCLC have not examined exosomal miRNAs, which could be expected to include the intact miRNA.…”

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

“…Robust studies evaluating circulating exosomal miRNAs signatures in esophageal cancer are yet to be reported, with the only recent studies limited to either esophageal squamous cell carcinoma cell lines, or a very small clinical cohort (eight individuals with esophageal adenocarcinoma vs. four controls) in which a broad discovery approach was not applied [13][14][15]. Hence, to evaluate the potential for circulating miRNAs in exosomes to be used as biomarkers for esophageal adenocarcinoma, we applied a broader discovery approach to investigate levels of circulating exosomal miRNAs in serum from individuals with esophageal adenocarcinoma, compared to non-dysplastic Barrett's esophagus and age-matched controls.…”