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

Molecular Cancer

Research

Xiao-Wei Wang¹  Xi-Lei Zhou²  Hai-Wei Xie³  Tong-Xin Yang³  Yu-Suo Tong³  Zi-Hao Liu³  Xiu-Feng Cao³  Jin Lv³  Wei-Hong Shi³  Qing-Quan Wu⁴ 

[1] Department of Medical Oncology, Huai’an First People’s Hospital Affiliated to Nanjing Medical University, Huai’an, Jiangsu, China;Department of Radiation Oncology, Huai’an First People’s Hospital Affiliated to Nanjing Medical University, Huai’an, Jiangsu, China;Department of Surgical Oncology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, Jiangsu, China;Department of Thoracic Surgery, Huai’an First People’s Hospital Affiliated to Nanjing Medical University, Huai’an, Jiangsu, China;

关键词: Esophageal cancer;    Long non-coding RNAs;    Plasma;    Biomarker;    Diagnosis;   

DOI  :  10.1186/1476-4598-14-3

 received in 2014-08-22, accepted in 2014-12-09,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundRecent 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.MethodsTen 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.ResultsESCC-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%).ConclusionsPlasma 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.

【 授权许可】

CC BY   
© Tong et al.; licensee BioMed Central. 2015