The results demonstrated that the levels of POU3F3, HNF1A-AS1 and SPRY4-IT1 were significantly higher in plasma from ESCC patients compared with normal controls, providing strong evidence that ESCC-related lncRNAs could be released into the circulation and that their different expression profiles in plasma could be used as diagnostic markers for ESCC. This evidence concerns the gene SPRY4 and esophageal squamous cell carcinoma.