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Background  Recent studies have demonstrated that long non-coding RNAs (lncRNAs) were present in the blood of cancer patients and have shown great potential as powerful and non-invasive tumor markers. However, little is known about the value of lncRNAs in the diagnosis of esophageal squamous cell carcinoma (ESCC). We hypothesized that ESCC-related lncRNAs might be released into the circulation during tumor initiation and could be utilized to detect and monitor ESCC.    Methods  Ten lncRNAs ( HOTAIR ,  AFAP1-AS1 ,  POU3F3 ,  HNF1A-AS1 ,  91H ,  PlncRNA1 ,  SPRY4-IT1 ,  ENST435885.1 ,  XLOC_013104  and  ENST547963.1 ) which previously found to be differently expressed in esophageal cancer were selected as candidate targets for subsequent circulating lncRNA assay. A four-stage exploratory study was conducted to test the hypothesis: (1) optimization of detected method to accurately and reproducibly measure ESCC-related lncRNAs in plasma and serum; (2) evaluation of the stability of circulating lncRNAs in human plasma or serum; (3) exploration the origin of ESCC-related lncRNAs in vitro and in vivo; (4) evaluation the diagnostic power of circulating lncRNAs for ESCC.    Results  ESCC-related lncRNAs were detectable and stable in plasma of cancer patients, and derived largely from ESCC tumor cells. Furthermore, plasma levels of  POU3F3 ,  HNF1A-AS1  and  SPRY4-IT1  were significantly higher in ESCC patients compared with normal controls. By receiver operating characteristic curve (ROC) analysis, among the three lncRNAs investigated, plasma  POU3F3  provided the highest diagnostic performance for detection of ESCC (the area under the ROC curve (AUC), 0.842;  p  < 0.001; sensitivity, 72.8%; specificity, 89.4%). Moreover, use of  POU3F3  and SCCA in combination could provide a more effective diagnosis performance (AUC, 0.926,  p  < 0.001, sensitivity, 85.7%; specificity, 81.4%). Most importantly, this combination was effective to detect ESCC at an early stage (80.8%).    Conclusions  Plasma  POU3F3  could serve as a potential biomarker for diagnosis of ESCC, and the combination of  POU3F3  and SCCA was more efficient for ESCC detection, in particular for early tumor screening.    Electronic supplementary material  The online version of this article (doi:10.1186/1476-4598-14-3) contains supplementary material, which is available to authorized users.

Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma