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Human IgG antibody profiles differentiate between symptomatic patients with and without colorectal cancer
  1. Gregor S Kijanka1,*,
  2. Suzanne Hector2,
  3. Elaine W Kay3,
  4. Frank Murray4,
  5. Robert Cummins3,
  6. Derek Murphy1,
  7. Brian D MacCraith5,
  8. Jochen HM Prehn6,
  9. Dermot Kenny7
  1. 1 Royal College of Surgeons, Centre for Human Proteomics, Ireland;
  2. 2 Royal College of Surgeons, Centre for Human Proteomics, Physiology & Medical Physics, Ireland;
  3. 3 Department of Pathology, Beaumont Hospital, Royal College of Surgeons, Ireland;
  4. 4 Department of Gastroenterology, Beaumont Hospital, Ireland;
  5. 5 Biomedical Diagnostics Institute, Dublin City University, Ireland;
  6. 6 Centre for Human Proteomics, Physiology & Medical Physics, Royal College of Surgeons, Ireland;
  7. 7 Clinical Research Centre, RCSI; Biomedical Diagnostics Institute, DCU, Ireland
  1. Correspondence to: Gregor Kijanka, Centre for Human Proteomics, Royal College of Surgeons in Ireland, 121 St Stephen's Green, Dublin 2, none, Republic of Ireland; gregor.kijanka{at}dcu.ie

Abstract

Objective: Patients with cancer have antibodies against tumour antigens. Characterizing the antibody repertoire may provide insights into aberrant cellular mechanisms in cancer development, ultimately leading to novel diagnostic or therapeutic targets. Here we set out to characterize the antibody profiles in patients whose symptoms warranted colonoscopy, to see if there was a difference in patients with and without colorectal cancer.

Methods: Patients were recruited from a colonoscopy clinic. Individual serum samples from 43 patients with colorectal cancer and 40 patients with no cancer on colonoscopy were profiled on a 37,830-clone recombinant human protein array. Antigen expression was evaluated by quantitative RT-PCR and by immunohistochemistry on tissue microarrays.

Results: Using a sex- and age-matched training set we identified and confirmed 18 antigens associated with cancer and 4 associated with the absence of cancer (p < 0.05). To investigate the mechanisms triggering antibody responses to these antigens, we examined antigen expression in normal colorectal mucosa and colorectal carcinoma of the same patients. The identified antigens showed cellular accumulation (p53), aberrant cellular expression (HMGB1) and overexpression (TRIM28, p53, HMGB1, TCF3, LASS5, ZN346) in colorectal cancer tissue compared to normal colorectal mucosa.

Conclusions: We demonstrate for the first time that screening high-density protein arrays identifies unique antibody profiles that discriminate between symptomatic patients with and without colorectal cancer. The differential expression of identified antigens suggests their involvement in aberrant cellular mechanisms in cancer.

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