title: Development of autoantibody signatures as biomarkers for early detection of colorectal carcinoma.
abstract: OBJECTIVE
  To select autoantibody signatures for early detection of colorectal cancer (CRC).
  
  
  METHODS
  A phage cDNA expression library was constructed with fresh tumors from 30 CRC patients and biopanned by using serum pools of 20 CRC patients and 20 healthy controls. A classifier was discovered in the training set of 30 CRC patients at stages I and II and 30 matched healthy controls and then blindly validated in an independent set of 60 CRC patients, 60 healthy controls, 52 polyps patients, and 30 autoimmune diseases patients. Expression of proteins was examined by using immunohistochemistry.
  
  
  RESULTS
  Five-phage peptide clones showing higher discriminatory power than others in training set were selected for validation. The five-phage peptide classifier was able to discriminate between early CRC patients and healthy controls, with sensitivities of 90.0% to 92.7% and specificities of 91.7% to 93.3%. In those with serum carcinoembryonic antigen less than 5 ng/mL, the classifier was efficient in discriminating CRC from healthy controls, with an area under the curve of 0.975. The classifier was able to discriminate all of the 9 patients with serrated adenoma from healthy controls. Thirteen (43.3%) of the patients with autoimmune diseases were misclassified. Of the five phage peptides, one encoded a peptide identical to immunoglobulin G (IgG) heavy-chain constant region. IgG immunostaining was stronger in mesenchymal cells than in cancer cells in the tumors and was apparent in serrated adenoma.
  
  
  CONCLUSIONS
  The five-phage peptide classifier stands out as promising early diagnostic biomarkers for CRC, but it is unsuitable for discriminating CRC from autoimmune diseases. Truncated IgGs generated from the tumors might be novel CRC-associated antigens.
authors.affiliation: Department of Epidemiology, College of Basic Medicine, First Affiliated Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Chang
authors.forename: Lingling
authors.initials: L
authors.lastname: Wu
authors.forename: Fuao
authors.initials: F
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Liye
authors.initials: L
authors.lastname: Ma
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Dongbao
authors.initials: D
authors.lastname: Zhao
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Tan
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Yu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lou
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhao
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Chuangang
authors.initials: C
authors.lastname: Fu
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
mesh_terms: D000236:Adenoma / Q000175:diagnosis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018951:Antigens, CD20 / Q000096:biosynthesis; D001323:Autoantibodies / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D017123:Bacteriophage T7 / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood; D003111:Colonic Polyps / Q000276:immunology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000276:immunology; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics; D007143:Immunoglobulin Heavy Chains; D008297:Male; D008875:Middle Aged; D019151:Peptide Library; D012680:Sensitivity and Specificity
chemical_list: D018951:Antigens, CD20; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D019151:Peptide Library