The differential expression of microRNAs (miRNAs) in plasma of esophageal squamous cell carcinoma (ESCC) patients may serve as a diagnostic biomarker. A four-stage study was conducted to identify plasma miRNAs with potential in detecting ESCC. Exiqon panels (2 ESCC pools vs. 1 normal control (NC) pool) were applied in the screening phase to obtain miRNA profiles. The identified miRNAs were further evaluated through training (36 ESCC VS. 42 NCs) and testing stages (101 ESCC VS. 113 NCs) with qRT-PCR assays. A six-miRNA signature including up-regulated miR-106a, miR-18a, miR-20b, miR-486-5p, miR-584 and down-regulated miR-223-3p in ESCC was identified. The signature could accurately discriminate ESCC patients from NCs with areas under the receiver operating characteristic curve of 0.935, 0.959 and 0.966 for the training, testing and the additional validation stage (41 ESCC VS. 50 NCs), respectively. MiR-106a and miR-584 were significantly up-regulated in tumor tissues with qRT-PCR assays. And miR-584 was also up-regulated in ESCC tissues from TCGA database. In addition, exosomal miR-223-3p and miR-584 were consistently dysregulated with those in plasma and could also act as biomarkers in diagnosis of ESCC. In conclusion, we identified a six-miRNA signature in plasma which could act as a non-invasive biomarker in detection of ESCC.
Keywords: TCGA; diagnosis; esophageal squamous cell carcinoma; exosomes; miRNA.