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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.

Tong YS, Wang XW, Zhou XL, Liu ZH, Yang TX, Shi WH, Xie HW, Lv J, Wu QQ, Cao XF - Mol. Cancer (2015)

Bottom Line: 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.Furthermore, plasma levels of POU3F3, HNF1A-AS1 and SPRY4-IT1 were significantly higher in ESCC patients compared with normal controls.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%).

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Oncology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. tongyusuo@163.com.

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.

No MeSH data available.


Related in: MedlinePlus

Evaluation of plasma lncRNAs for detection of ESCC. Receiver operating characteristics (ROC) curves were drawn with the data of plasma lncRNAs from 147 patients with ESCC and 123 healthy controls. (A-D) ROC-AUC for detecting ESCC from healthy controls (POU3F3, 0.842, p < 0.001; HNF1A-AS1, 0.781, p < 0.001; SPRY4-IT1, 0.800, p < 0.001; SCCA, 0.784, p < 0.001).
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Fig6: Evaluation of plasma lncRNAs for detection of ESCC. Receiver operating characteristics (ROC) curves were drawn with the data of plasma lncRNAs from 147 patients with ESCC and 123 healthy controls. (A-D) ROC-AUC for detecting ESCC from healthy controls (POU3F3, 0.842, p < 0.001; HNF1A-AS1, 0.781, p < 0.001; SPRY4-IT1, 0.800, p < 0.001; SCCA, 0.784, p < 0.001).

Mentions: To investigate the characteristics of the three ESCC-related lncRNAs as potential tumor markers of ESCC, Receiver operating characteristics (ROC) curves and the area under the ROC curves (AUC) were performed on data from all subjects, including 147 ESCC patients and 123 healthy donors. The ROC curves illustrated strong separation between the ESCC patients and control group, with an AUC of 0.842 (95% CI: 0.794 – 0.890; p < 0.001) for POU3F3, 0.781 (95% CI: 0.727 – 0.835: p < 0.001) for HNF1A-AS1, and 0.800 (95% CI: 0.748 – 0.853: p < 0.001) for SPRY4-IT1, respectively, compared with classic tumor marker SCCA (ng/ml) with an AUC of 0.784 (95% CI: 0.727 – 0.841; p < 0.001) (Figure 6). Moreover, plasma level of POU3F3 could discriminate ESCC from normal controls with 72.8% sensitivity and 89.4% specificity, although the levels of HNF1A-AS1 and SPRY4-IT1 in plasma were less sensitive (32.7% and 48.2%) for ESCC detection. Therefore, of the three lncRNAs in this analysis, POU3F3 provided the highest diagnostic power for the detection of ESCC, suggesting that plasma POU3F3 could serve as a promising tumor marker for ESCC diagnosis.Figure 6


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

Tong YS, Wang XW, Zhou XL, Liu ZH, Yang TX, Shi WH, Xie HW, Lv J, Wu QQ, Cao XF - Mol. Cancer (2015)

Evaluation of plasma lncRNAs for detection of ESCC. Receiver operating characteristics (ROC) curves were drawn with the data of plasma lncRNAs from 147 patients with ESCC and 123 healthy controls. (A-D) ROC-AUC for detecting ESCC from healthy controls (POU3F3, 0.842, p < 0.001; HNF1A-AS1, 0.781, p < 0.001; SPRY4-IT1, 0.800, p < 0.001; SCCA, 0.784, p < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4631113&req=5

Fig6: Evaluation of plasma lncRNAs for detection of ESCC. Receiver operating characteristics (ROC) curves were drawn with the data of plasma lncRNAs from 147 patients with ESCC and 123 healthy controls. (A-D) ROC-AUC for detecting ESCC from healthy controls (POU3F3, 0.842, p < 0.001; HNF1A-AS1, 0.781, p < 0.001; SPRY4-IT1, 0.800, p < 0.001; SCCA, 0.784, p < 0.001).
Mentions: To investigate the characteristics of the three ESCC-related lncRNAs as potential tumor markers of ESCC, Receiver operating characteristics (ROC) curves and the area under the ROC curves (AUC) were performed on data from all subjects, including 147 ESCC patients and 123 healthy donors. The ROC curves illustrated strong separation between the ESCC patients and control group, with an AUC of 0.842 (95% CI: 0.794 – 0.890; p < 0.001) for POU3F3, 0.781 (95% CI: 0.727 – 0.835: p < 0.001) for HNF1A-AS1, and 0.800 (95% CI: 0.748 – 0.853: p < 0.001) for SPRY4-IT1, respectively, compared with classic tumor marker SCCA (ng/ml) with an AUC of 0.784 (95% CI: 0.727 – 0.841; p < 0.001) (Figure 6). Moreover, plasma level of POU3F3 could discriminate ESCC from normal controls with 72.8% sensitivity and 89.4% specificity, although the levels of HNF1A-AS1 and SPRY4-IT1 in plasma were less sensitive (32.7% and 48.2%) for ESCC detection. Therefore, of the three lncRNAs in this analysis, POU3F3 provided the highest diagnostic power for the detection of ESCC, suggesting that plasma POU3F3 could serve as a promising tumor marker for ESCC diagnosis.Figure 6

Bottom Line: 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.Furthermore, plasma levels of POU3F3, HNF1A-AS1 and SPRY4-IT1 were significantly higher in ESCC patients compared with normal controls.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%).

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Oncology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. tongyusuo@163.com.

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.

No MeSH data available.


Related in: MedlinePlus