Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma

Background MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer. Methods Serum samples from patients with esophageal squamous cell carcinoma (ESCC) and age and sex matched healthy control (HC) individuals were investigated for the expression of miR/isomiRs using NGS. Candidate miR/isomiRs which met the criteria in the 1st group (ESCC = 18 and HC = 12) were validated in the 2nd group (ESCC = 30 and HC = 30). A diagnostic panel was generated using miR/isomiRs that were consistently confirmed in the 1st and 2nd groups. Accuracy of the panel was tested then in the 3rd group (ESCC = 18 and HC = 18). Their use was also investigated in 22 paired samples obtained pre- and post-treatment, and in patients with esophageal adenocarcinoma (EAD) and high‐grade dysplasia (HGD). Results Twenty-four miR/isomiRs met the criteria for diagnostic biomarker in the 1st and 2nd group. A multiple regression model selected one mature miR (miR-30a-5p) and two isomiRs (isoform of miR-574-3p and miR-205-5p). The index calculated from the diagnostic panel was significantly higher in ESCC patients than in the HCs (13.3±8.9 vs. 3.1±1.3, p