title: Association of insulin-like growth factor-binding protein-3 with radiotherapy response and prognosis of esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Insulin-like growth factor-binding protein-3 (IGFBP-3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma (ESCC). The present study was designed to investigate the clinical and prognostic effects of IGFBP-3 on ESCC.
  
  
  METHODS
  IGFBP-3 was detected by immunohistochemistry in paraffin-embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non-malignant esophageal specimens. Receiver operating characteristic (ROC) analysis was used to determine cut-off scores for tumor positivity and to evaluate patient survival status. The χ(2) test was performed to analyze the association of IGFBP-3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP-3 expression were investigated using Kaplan-Meier analysis and the Cox proportional hazards model.
  
  
  RESULTS
  The threshold for IGFBP-3 positivity was set to greater than 65% [area under the ROC curve (AUC)=0.690, P<0.019]. Of the 70 ESCC patient tissues tested, 32 (45.7%) were defined as having high IGFBP-3 expression. The levels of IGFBP-3 protein expression were decreased in 70.0% (7 of 10) of ESCC tissues compared with adjacent non-malignant esophageal tissue. In addition, IGFBP-3 expression was associated with pathologic classification (P<0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP-3 in the tumor had an improved radiotherapy response and prolonged overall survival (P<0.001).
  
  
  CONCLUSIONS
  High level of IGFBP-3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. luolil@sysucc.org.cn.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P.R. China. luolil@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. luolil@sysucc.org.cn.
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Luo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. zhaolei@sysucc.org.cn.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P.R. China. zhaolei@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. zhaolei@sysucc.org.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. ximian@sysucc.org.cn.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P.R. China. ximian@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. ximian@sysucc.org.cn.
authors.forename: Mian
authors.initials: M
authors.lastname: Xi
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. helir@sysucc.org.cn.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P.R. China. helir@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. helir@sysucc.org.cn.
authors.forename: Li-Ru
authors.initials: LR
authors.lastname: He
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. shenjx@sysucc.org.cn.|Medical Imaging and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P.R. China. shenjx@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. shenjx@sysucc.org.cn.
authors.forename: Jing-Xian
authors.initials: JX
authors.lastname: Shen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. liqq@sysucc.org.cn.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P.R. China. liqq@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. liqq@sysucc.org.cn.
authors.forename: Qiao-Qiao
authors.initials: QQ
authors.lastname: Li
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. liushil@sysucc.org.cn.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P.R. China. liushil@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. liushil@sysucc.org.cn.
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. zhangpeng@sysucc.org.cn.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P.R. China. zhangpeng@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. zhangpeng@sysucc.org.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. xiedan@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. xiedan@sysucc.org.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. liumengzhong@126.com.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P.R. China. liumengzhong@126.com.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P.R. China. liumengzhong@126.com.
authors.forename: Meng-Zhong
authors.initials: MZ
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell; D004938:Esophageal Neoplasms; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D007150:Immunohistochemistry; D018972:Insulin-Like Growth Factor Binding Protein 3; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D011838:Radiation-Sensitizing Agents
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D011838:Radiation-Sensitizing Agents