Identification of Novel Circulating miRNA Biomarkers for the Diagnosis of Esophageal Squamous Cell Carcinoma and Squamous Dysplasia

Background: Circulating miRNAs have been identified as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC), but their efficacy in discovering early-stage ESCC is still unsatisfying. Esophageal squamous dysplasia (ESD) is the precursor lesion of ESCC. Notably, little is known about the role(s) of circulating miRNAs in identifying ESD. In this study, we, therefore, aimed to identify serum miRNAs as novel diagnostic markers for detecting ESD and ESCC. Methods: The genome-wide miRNA expression was profiled in 104 (52 ESCC and 52 controls) serum samples using microarray. Seven candidate miRNAs from the microarray assay were evaluated for their diagnostic performance in another cohort of 266 participants (96 ESCC, 92 ESD, and 78 healthy controls). Results: The serum levels of miR-16-5p, miR-197-5p, miR-451a, and miR-92a-3p were associated with ESCC; the biomarker based on the panel of these four miRNAs could efficiently distinguish patients with ESCC from the controls [AUC = 0.856; 95% confidence interval (CI), 0.794-0.905; P < 0.001]. The serum levels of miR-16-5p, miR-320c, miR-638, and miR-92a-3p were significantly higher in patients with ESD than in controls, and this four-miRNA signature could efficiently differentiate patients with ESD from the controls (AUC = 0.842; 95% CI, 0.778-0.893; P < 0.001). In addition, compared with serum carcinoembryonic antigen and carbohydrate antigen 199, miRNA-based panels had a better diagnostic performance in distinguishing patients with ESCC and ESD from healthy controls. Conclusions: Our study identified two novel panels of circulating miRNAs with high efficiency in detecting ESCC and ESD, suggesting that circulating miRNAs, in particular the combination of them, might serve as noninvasive biomarkers for the early detection of ESCC. Impact: This study suggests the feasibility of using circular miRNA-based blood tests to aid in the detection of ESD and ESCC.