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Dear Editor, Endoscopy with iodine staining was widely used for esophageal cancer (EC) screening in high-incidence area.1,2 Most endoscopy screening-positive population was found to develop esophageal epithelium lesion, and therefore endured higher risk for developing esophageal squamous cell carcinoma (ESCC) than normal population.3,4 However, endoscopic screening may be too costly and invasive for large-scale population, and non-invasive biomarkers may be more applicable and cost effective for population-based screening.5,6 In this population-based screening study, we aim to identify potential metabolic biomarkers for early screening of ESCC, and establish the optimal early ESCC screening model. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was used to explore ESCC screening related metabolic biomarkers and profile difference between ESCC screening-positive subjects and normal population. [Extracted from the article]