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Sensitive and specific biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) are urgently needed to reduce the high morbidity and high mortality of the disease.The discovery of serum microRNAs (miRNAs) and their unique expression profile in patients with various diseases makes them an attractive, novel non-invasive biomarker for tumor diagnosis.In this study, we determined the serum miRNA expression profile in ESCC patients to develop a novel diagnostic ESCC biomarker.Serum samples were from 290 ESCC patients and 140 age-and gender-matched controls.