Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma
The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for improved detection methods. The potential for circulating microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating miRNAs have not been well characterized in esophageal adenocarcinoma. We investigated whether circulating exosomal miRNAs have potential to discriminate individuals with esophageal adenocarcinoma from healthy controls and non-dysplastic Barrett’s esophagus.
Seven hundred fifty-eight miRNAs were profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10 individuals with Barrett’s esophagus, and 18 individuals with locally advanced esophageal adenocarcinoma. MiRNA expression was assessed using all possible permutations of miRNA ratios per individual. Four hundred eight miRNA ratios were differentially expressed in individuals with cancer compared to controls and Barrett’s esophagus (Mann-Whitney U test, P < 0.05). The 179/408 ratios discriminated esophageal adenocarcinoma from healthy controls and Barrett’s esophagus (linear regression, P < 0.05; area under receiver operating characteristic (ROC) > 0.7, P < 0.05). A multi-biomarker panel (RNU6-1/miR-16-5p, miR-25-3p/miR-320a, let-7e-5p/miR-15b-5p, miR-30a-5p/miR-324-5p, miR-17-5p/miR-194-5p) demonstrated enhanced specificity and sensitivity (area under ROC = 0.99, 95 % CI 0.96–1.0) over single miRNA ratios to distinguish esophageal adenocarcinoma from controls and Barrett’s esophagus.
This study highlights the potential for serum exosomal miRNAs as biomarkers for the detection of esophageal adenocarcinoma.
KeywordsEsophageal cancer Barrett’s esophagus Biomarkers microRNAs Exosomes Serum
- 2.Dubecz, A., et al., Does the Incidence of Adenocarcinoma of the Esophagus and Gastric Cardia Continue to Rise in the Twenty-First Century?-a SEER Database Analysis. J Gastrointest Surg, 2013.Google Scholar
- 10.Cheng, L., et al., Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J Extracell Vesicles, 2014. 3.Google Scholar
- 15.Warnecke-Eberz, U., et al., Exosomal onco-miRs from serum of patients with adenocarcinoma of the esophagus: comparison of miRNA profiles of exosomes and matching tumor. Tumour Biol, 2015.Google Scholar