Serum exosomal micrornas as clinical biomarkers for the detection of Barrett's esophagus and esophageal adenocarcinoma

• Main Author: Nwachokor, Jasmin A
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2015
• Subjects: Medicine; Molecular biology; Pathology
• ISBN: 9781321947410; 1321947410

Background: Barrett’s esophagus (BE), caused by Gastroesophageal Reflux Disease (GERD), is the main premalignant condition for esophageal adenocarcinoma (EAC). The majority of BE and EAC patients are missed or diagnosed late resulting in dismal outcomes. Multiple studies have proposed serum microRNAs (miRNAs) as promising biomarkers for benign and malignant conditions. MicroRNAs contained in serum exosomes have increased stability and are a unique, non-invasive strategy for BE and EAC diagnosis. Methods: Serum from patients with GERD, BE and EAC (n=8 each) were differentially centrifuged to isolate exosomes. RNA was extracted with Trizol and next-generation sequencing was performed on the Illumina HiSeq2500 Sequencing platform. Analysis of the data was conducted using mirDeep2/EdgeR and prediction classification analysis. A False Discovery Rate (FDR) < 0.05 was considered significant.
Results: All subjects were white males with the following mean ages: GERD: 58±9 years; BE: 63±8 years; EAC: 64±3 years (p=0.3833). Comparison of serum exosomal miRNA profiles among the 3 groups found most significant differences between EAC patients compared to BE and GERD patients (79 and 85 miRNAs were found in EAC vs BE and GERD, respectively). Comparison of BE versus GERD patients found 17 differentially expressed serum exosomal miRNAs. Additionally, for each of the disease comparisons, approximately half of the significant miRNAs were up-regulated and the half were down-regulated. Prediction analysis identified a signature of 34 miRNAs that could be used to distinguish these conditions. Conclusion: We have identified promising candidate serum miRNAs for distinguishing GERD patients with and without BE and EAC. These findings need to be further validated to develop blood-based assays for clinical use.