title: A protein fragment derived from DNA-topoisomerase I as a novel tumour-associated antigen for the detection of early stage carcinoma.
abstract: BACKGROUND
  The production of autoantibodies against tumour-associated antigens (TAAs) is believed to reflect greater immunologic reactivity in cancer patients and enhanced immune surveillance for cancer cells. Over the past few decades, a number of different TAAs and their corresponding autoantibodies have been investigated. However, positive frequency of autoantibody detection in cancer patients has been relatively low. Here we describe a novel TAA that was a fragment derived from human DNA-topoiomerase I and an autoantibody against the novel TAA with relatively high positive frequency in the sera of early-stage non-small-cell lung cancer (NSCLC), gastric cancer (GC), colorectal cancer (CRC) and oesophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  Serologic enzyme-linked immunosorbent assay (ELISA) and western blot were used to discover a novel TAA with a molecular weight of 48 kDa separated by ion exchange chromatography. Autoantibody ELISA, immnohistochemistry and immunofluorescent staining, recombinant protein cloning/expression and western blot were used to identify the novel TAA. The association of the autoantibody against the novel TAA with early-stage carcinoma was explored by screening 203 stage I/II patients and 170 stage III/IV patients with NSCLC, GC, CRC or ESCC.
  
  
  RESULTS
  We identified the novel TAA as a fragment derived from human DNA-topoiomerase I (TOP1). We found that the novel TAA induced specific autoantibodies with a high prevalence that ranged from 58 to 72% in some of the most common types of cancer. We observed that the immune response against the novel TAA was associated with early stage ESCC, GC, CRC and NSCLC.
  
  
  CONCLUSIONS
  The findings in this study suggest that the autoantibody against the novel TAA may be a potential biomarker for use in the early detection and diagnosis of cancer.
authors.affiliation: Chengdu Cancer Bioengineering Research Institute, 37 Twelve Bridge Road, Chengdu 610075, Sichuan, PR China.|Chengdu Geimmica Scientific Ltd, Chengdu, Sichuan, PR China.|Department of Oncology, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, PR China.
authors.forename: Shang-Mian
authors.initials: SM
authors.lastname: Yie
authors.affiliation: Chengdu Cancer Bioengineering Research Institute, 37 Twelve Bridge Road, Chengdu 610075, Sichuan, PR China.|Chengdu Geimmica Scientific Ltd, Chengdu, Sichuan, PR China.
authors.forename: Shang-Rong
authors.initials: SR
authors.lastname: Ye
authors.affiliation: Chengdu Geimmica Scientific Ltd, Chengdu, Sichuan, PR China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Ma
authors.affiliation: Department of Oncology, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xie
authors.affiliation: Core Laboratory, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, PR China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Zhang
authors.affiliation: Core Laboratory, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Cao
authors.affiliation: Core Laboratory, Sichuan Academy of Medical Sciences, Chengdu, Sichuan, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: He
authors.affiliation: Laboratory of Stem Cells and Regeneration Medicine, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong, PR China.
authors.forename: Zhen-Bo
authors.initials: ZB
authors.lastname: Hu
authors.affiliation: Chengdu Geimmica Scientific Ltd, Chengdu, Sichuan, PR China.
authors.forename: Cheng-Lu
authors.initials: CL
authors.lastname: Yang
authors.affiliation: Chengdu Geimmica Scientific Ltd, Chengdu, Sichuan, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Chengdu Geimmica Scientific Ltd, Chengdu, Sichuan, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zeng
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D004264:DNA Topoisomerases, Type I