title: Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma.
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.
authors.affiliation: Department of Surgical Oncology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. tongyusuo@163.com.
authors.forename: Yu-Suo
authors.initials: YS
authors.lastname: Tong
authors.affiliation: Department of Medical Oncology, Huai'an First People's Hospital Affiliated to Nanjing Medical University, Huai'an, Jiangsu, China. wxw7354@sina.com.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Huai'an First People's Hospital Affiliated to Nanjing Medical University, Huai'an, Jiangsu, China. zhouxilei1226@163.com.
authors.forename: Xi-Lei
authors.initials: XL
authors.lastname: Zhou
authors.affiliation: Department of Surgical Oncology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. lzh5664@126.com.
authors.forename: Zi-Hao
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: Department of Surgical Oncology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. 823947824@qq.com.
authors.forename: Tong-Xin
authors.initials: TX
authors.lastname: Yang
authors.affiliation: Department of Surgical Oncology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. shiweihong9@yahoo.com.cn.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Shi
authors.affiliation: Department of Surgical Oncology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. xhw8502@163.com.
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Xie
authors.affiliation: Department of Surgical Oncology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. lvjin1978@sina.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital Affiliated to Nanjing Medical University, Huai'an, Jiangsu, China. wqq1120@sina.com.
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Wu
authors.affiliation: Department of Surgical Oncology, Nanjing Frist Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. cxf551101@sina.com.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Cao
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009367:Neoplasm Staging; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000097:blood*; D012372:ROC Curve; D015203:Reproducibility of Results; D015843:Serpins / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D015843:Serpins; C051072:squamous cell carcinoma-related antigen