Circulating MicroRNAs in Relation to Esophageal Adenocarcinoma Diagnosis and Survival

Background and Aims Tissue miRNA can discriminate between esophageal adenocarcinoma (EA) and normal epithelium. However, no studies have examined a comprehensive panel of circulating miRNAs in relation to EA diagnosis and survival. Methods We used all 62 EA cases from the US Multi-Center case–control study with available serum matched 1:1 to controls. Cases were followed for vital status. MiRNAs ( n = 2064) were assessed using the HTG EdgeSeq miRNA Whole Transcriptome Assay. Differential expression analysis of miRNAs in relation to case–control status was conducted. In cases, Cox regression models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. P values were adjusted using the Benjamini–Hochberg (BH) procedure for false discovery rate control. Predictive performance was assessed using cross-validation. Results Sixty-eight distinct miRNAs were significantly upregulated between cases and controls (e.g., miR-1255b-2-3p fold change = 1.74, BH-adjusted P = 0.01). Assessing the predictive performance of these significantly upregulated miRNAs yielded 60% sensitivity, 65% specificity, and 0.62 AUC. miR-4253 and miR-1238-5p were associated with risk of mortality after EA diagnosis (HR = 4.85, 95% CI: 2.30–10.23, BH-adjusted P = 0.04 and HR = 3.81, 95% CI: 2.02–7.19, BH-adjusted P = 0.04, respectively). Conclusions While they require replication, these findings suggest that circulating miRNAs may be associated with EA diagnosis and survival.