Abstract

MicroRNAs (miRNAs) may contribute to the initiation and progression of cancer. The role of circulating miRNAs as predictors of recurrence in esophageal adenocarcinoma (EAC) has not been extensively explored. Here we measured the expressions of 167 miRNAs in serum samples from a discovery cohort of 72 EAC patients (32 patients with recurrence and 40 patients without). A rank sum test was performed to identify differentially expressed miRNAs. Cox regression model was applied to estimate the effect of miRNA expression on recurrence-free survival. The eligible miRNAs were then validated in an independent cohort of 329 EAC patients (132 patients with recurrence and 197 patients without). miR-331-3p was identified and confirmed to be differentially expressed between EAC patients with and without recurrence and associated with recurrence-free survival. In both cohorts, the expression of miR-331-3p was consistently decreased in patients with recurrence compared to those without (P < 0.05). Using patients with low expression of miR-331-3p as reference, those with high expression had HRs for recurrence of 0.45 (95% CI, 0.21-0.96, P = 0.040) and 0.55 (95% CI, 0.38–0.78, P = 0.001) in the discovery and validation cohorts, respectively. Therefore, serum miR-331–3p may be a useful biomarker for identifying EAC patients at high risk of recurrence.

Highlights

  • Esophageal adenocarcinoma (EAC) is a fatal disease that is increasing in incidence[1] and that currently accounts for over 60% of the new esophageal cancer cases in the United States[2]

  • A number of studies have investigated the role of circulating miRNAs as prognostic indicators in EAC13 and esophageal squamous cell carcinoma[14,15,16]

  • We screened for serum miRNAs that are differentially expressed in esophageal adenocarcinoma (EAC) patients with and without recurrence, and investigated their association with recurrence-free survival

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Summary

Introduction

Esophageal adenocarcinoma (EAC) is a fatal disease that is increasing in incidence[1] and that currently accounts for over 60% of the new esophageal cancer cases in the United States[2]. MicroRNAs (miRNAs) are small non-coding RNAs at a length of 18–25 nucleotides[6]. They are very powerful regulators capable of simultaneously influencing the expression of hundreds of genes by binding to the target messenger RNAs (mRNAs), resulting in either mRNA degradation or translation inhibition[7]. A number of studies have investigated the role of circulating miRNAs as prognostic indicators in EAC13 and esophageal squamous cell carcinoma[14,15,16]. We screened for serum miRNAs that are differentially expressed in EAC patients with and without recurrence, and investigated their association with recurrence-free survival. Our aim was to explore the potential use of serum miRNAs as biomarkers for EAC recurrence

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