Serum miR-331-3p predicts tumor recurrence in esophageal adenocarcinoma

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.

Figure 1

Expression levels of candidate miRNA biomarkers in the discovery phase. The Y axis shows expression levels on a log 10 scale. Levels of serum miR-222-3p, miR-30c-5p, miR-19b, miR-29c-5p, miR-152-3p, miR-451a, miR-30d-5p, miR-92a-3p, miR-331-3p, and miR-25-3p were compared between recurrent (R) and non-recurrent (NR) patients with esophageal adenocarcinoma. Statistical analyses were performed using a rank sum test.

Figure 2

Expression levels of miR-30c-5p, miR-152-3p, miR-331-3p, and miR-25-3p in the validation phase. The Y axis shows expression levels on a log 10 scale. Levels of serum miRNAs were compared between recurrent (R) and non-recurrent (NR) patients with esophageal adenocarcinoma. A rank sum test was performed to compare groups.

Figure 3

Kaplan-Meier curves for recurrence-free survival in the discovery (A) and validation (B) cohorts grouped by low and high levels of serum miR-331-3p. N = number of patients with an event (recurrence)/total number of patients in the dataset. MRFS, median recurrence-free survival time in months.