Recent studies have reported that serum microRNAs (miRNAs) are potentially useful biomarkers for diagnosis and treatment of cancer. However, its utility for detecting esophageal squamous cell carcinoma (ESCC) has not been investigated yet. The aims of this study are to identify circulating serum miRNAs for ESCC detection.
We comprehensively analyzed serum miRNA expression profiles of 595 patients with ESCC, and 5051 non-cancer individuals using microarray (3D-Gene, Toray). Serum of non-cancer individuals was obtained from Biobank of NCGG and Health check up clinic (Yokohama Minoru clinic). Serum of ESCC patients was collected before starting any treatment such as radiotherapy, surgery and chemotherapy. Analyzed samples were randomly divided into discovery and validation sets. Serum miRNA levels were compared between ESCC and non-ESCC patients. Fisher’s linear discriminant analysis was performed to construct the discriminant model for ESCC detection. Measured values of each miRNAs were extrapolated into the discriminant formulas. We performed ROC analysis to evaluate the diagnostic ability of these formulas in each validation cohort.
In discovery set, 300 patients of ESCC was compared to 300 individuals of non-cancer control. We picked up 3 miRNAs, named miR-A, miR-B and miR-C, for ESCC diagnosis. Their AUC for detection of ESCC was 0.967, 0.873 and 0.650, respectively in ROC analysis. We constructed the discriminant model, called EC index, using these 3 miRNAs in discovery set. In validation set which contain 295 pts of ESCC and 4751 person of non-cancer control, EC index showed the AUC, sensitivity and specificity of the discriminant formula was 0.99, 0.98 and 0.95, respectively.
We identified novel serum miRNAs for ESCC detection. Our discriminant using these miRNAs can diagnose ESCC.
Clinical trial identification
Legal entity responsible for the study
National Cancer Center
Japan Agency for Medical Research and Development
K. Kato: Research fund: ONO, MSD, Shionogi. J. Kawauchi, S. Takizawa: Employee of Tray company. T. Ochiya: Grant/Research funding from: Kyowa Medex, Kewpie Corporation, Takeda, Rohto Pharmaceutical Co., Ltd., Japan Atherosclerosis Research Foundation, Inter Stem, BioMimetics Sympathies. All other authors have declared no conflicts of interest.