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Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma.
- Source :
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Molecular cancer [Mol Cancer] 2015 Jan 21; Vol. 14, pp. 3. Date of Electronic Publication: 2015 Jan 21. - Publication Year :
- 2015
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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.<br />Methods: Ten lncRNAs (HOTAIR, AFAP1-AS1, POU3F3, HNF1A-AS1, 91H, PlncRNA1, SPRY4-IT1, ENST00000435885.1, XLOC&#95;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.<br />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; pā<ā0.001; sensitivity, 72.8%; specificity, 89.4%). Moreover, use of POU3F3 and SCCA in combination could provide a more effective diagnosis performance (AUC, 0.926, pā<ā0.001, sensitivity, 85.7%; specificity, 81.4%). Most importantly, this combination was effective to detect ESCC at an early stage (80.8%).<br />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.
- Subjects :
- Animals
Antigens, Neoplasm metabolism
Carcinoma, Squamous Cell genetics
Carcinoma, Squamous Cell pathology
Case-Control Studies
Esophageal Neoplasms genetics
Esophageal Neoplasms pathology
Esophageal Squamous Cell Carcinoma
Gene Expression Regulation, Neoplastic
Humans
Mice, Inbred BALB C
Mice, Nude
Neoplasm Staging
RNA Stability
ROC Curve
Reproducibility of Results
Serpins metabolism
Biomarkers, Tumor blood
Carcinoma, Squamous Cell blood
Carcinoma, Squamous Cell diagnosis
Esophageal Neoplasms blood
Esophageal Neoplasms diagnosis
RNA, Long Noncoding blood
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4598
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- Molecular cancer
- Publication Type :
- Academic Journal
- Accession number :
- 25608466
- Full Text :
- https://doi.org/10.1186/1476-4598-14-3