Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma
Research
Molecular Cancer 2015, 14:3Â
doi:10.1186/1476-4598-14-3
Published: 21 January 2015
Abstract (provisional)
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.