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01.12.2015 | Research | Ausgabe 1/2015 Open Access

Molecular Cancer 1/2015

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

Zeitschrift:
Molecular Cancer > Ausgabe 1/2015
Autoren:
Yu-Suo Tong, Xiao-Wei Wang, Xi-Lei Zhou, Zi-Hao Liu, Tong-Xin Yang, Wei-Hong Shi, Hai-Wei Xie, Jin Lv, Qing-Quan Wu, Xiu-Feng Cao
Wichtige Hinweise

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.

Competing interests

The authors declare that they have no conflict of interests.

Authors’ contributions

X.C. and Y.T. conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript, X.Z. conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; X.W., Z.L., T.Y., and W.S. data analysis and interpretation; J.L., H.X. and Q.W. provision of study materials. All authors read and approved the final manuscript.

Abstract

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, ENST00000435885.1, XLOC_013104 and ENST00000547963.1) 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.
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