title: ANO1 protein as a potential biomarker for esophageal cancer prognosis and precancerous lesion development prediction.
abstract: OBJECTIVE
  Anoctamin 1 (ANO1) has been found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous study. Herein we showed the clinical relevance of ANO1 alterations with ESCC and esophageal precancerous lesion progression.
  
  
  RESULTS
  ANO1 was detected in 38.1% (109/286) and 25.4% (77/303) of tumors in the two cohorts, but in none of morphologically normal operative margin tissues. ANO1 expression was significantly associated with a shorter overall survival (OS), especially in patients with moderately differentiated and stage IIA tumors. In 499 iodine-unstained biopsies from the endoscopic screening cohort in 2005-2007, all the 72 pathologically normal epithelial mucosa presented negative immunostaining, whereas ANO1 expression was observed in 3/11 tumors and 5/231 intraepithelial lesions. 7/8 ANO1-positive cases had developed unfavorable outcomes revealed by endoscopic follow-up in 2012. Analysis of another independent cohort of 148 intraepithelial lesions further confirmed the correlation between ANO1 expression and progression of precancerous lesions. 3/4 intraepithelial lesions with ANO1 expression had developed ESCC within 4-9 years after the initial endoscopic examination.
  
  
  METHODS
  Immunohistochemistry (IHC) was performed to examine ANO1 expression in surgical ESCC specimens and two independent cohorts of esophageal biopsies from endoscopic screening in high-incidence area of ESCC in northern China. Association between ANO1 expression, clinico-pathologic parameters, and the impact on overall survival was analyzed.
  
  
  CONCLUSIONS
  Positive ANO1 is a promising biomarker to predict the unfavorable outcome for ESCC patients. More importantly, it can predict disease progression of precancerous lesions.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Hao
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450000, China.
authors.forename: Xue-Ke
authors.initials: XK
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: He
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Zhi-Zhou
authors.initials: ZZ
authors.lastname: Shi
authors.affiliation: Department of Histology and Embryology, Anhui Medical University, Hefei 230032, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Anqing City Hospital, Affiliated Anqing Hospital of Anhui Medical University, Anqing 246003, China.
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Yi-Zhen
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Tong-Tong
authors.initials: TT
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Histology and Embryology, Anhui Medical University, Hefei 230032, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Jia
authors.affiliation: Department of Gastroenterology, Anqing City Hospital, Affiliated Anqing Hospital of Anhui Medical University, Anqing 246003, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Qi-Min
authors.initials: QM
authors.lastname: Zhan
authors.affiliation: Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China.
authors.forename: En-Min
authors.initials: EM
authors.lastname: Li
authors.affiliation: Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450000, China.
authors.forename: Li-Dong
authors.initials: LD
authors.lastname: Wang
authors.affiliation: Department of Cancer Epidemiology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Wen-Qiang
authors.initials: WQ
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Wang
mesh_terms: D000075369:Anoctamin-1 / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: ANO1; biomarker; esophageal squamous cell carcinoma; precancerous lesions; prognosis