title: Human Blood Autoantibodies in the Detection of Colorectal Cancer.
abstract: Colorectal cancer (CRC) is the second most common malignancy in the western world. Early detection and diagnosis of all cancer types is vital to improved prognosis by enabling early treatment when tumours should be both resectable and curable. Sera from 3 different cohorts; 42 sera (21 CRC and 21 matched controls) from New York, USA, 200 sera from Pittsburgh, USA (100 CRC and 100 controls) and 20 sera from Dundee, UK (10 CRC and 10 controls) were tested against a panel of multiple tumour-associated antigens (TAAs) using an optimised multiplex microarray system. TAA specific IgG responses were interpolated against the internal IgG standard curve for each sample. Individual TAA specific responses were examined in each cohort to determine cutoffs for a robust initial scoring method to establish sensitivity and specificity. Sensitivity and specificity of combinations of TAAs provided good discrimination between cancer-positive and normal serum. The overall sensitivity and specificity of the sample sets tested against a panel of 32 TAAs were 61.1% and 80.9% respectively for 6 antigens; p53, AFP, K RAS, Annexin, RAF1 and NY-CO16. Furthermore, the observed sensitivity in Pittsburgh sample set in different clinical stages of CRC; stage I (n = 19), stage II (n = 40), stage III (n = 34) and stage IV (n = 6) was similar (73.6%, 75.0%, 73.5% and 83.3%, respectively), with similar levels of sensitivity for right and left sided CRC. We identified an antigen panel of sufficient sensitivity and specificity for early detection of CRC, based upon serum profiling of autoantibody response using a robust multiplex antigen microarray technology. This opens the possibility of a blood test for screening and detection of early colorectal cancer. However this panel will require further validation studies before they can be proposed for clinical practice.
authors.affiliation: Immunology, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.|Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Ola H
authors.initials: OH
authors.lastname: Negm
authors.affiliation: School of Medicine, University of Nottingham, Derby, United Kingdom.|Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Hamed
authors.affiliation: University of Pittsburgh, School of Medicine, Pittsburgh, United States of America.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schoen
authors.affiliation: Mount Sinai Roosevelt, Division of Colon and Rectal Surgery, Department of Surgery, New York, United States of America.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Whelan
authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Steele
authors.affiliation: Nottingham Digestive Diseases Centre, Nottingham University Hospital, Nottingham, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Scholefield
authors.affiliation: Immunology, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Dilnot
authors.affiliation: Mount Sinai Roosevelt, Division of Colon and Rectal Surgery, Department of Surgery, New York, United States of America.
authors.forename: H M C
authors.initials: HM
authors.lastname: Shantha Kumara
authors.affiliation: School of Medicine, University of Nottingham, Derby, United Kingdom.
authors.forename: John F R
authors.initials: JF
authors.lastname: Robertson
authors.affiliation: Immunology, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Herbert F
authors.initials: HF
authors.lastname: Sewell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017305:Annexin A1 / Q000097:blood / Q000276:immunology; D000951:Antigens, Neoplasm / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019908:Proto-Oncogene Proteins c-raf / Q000097:blood / Q000276:immunology; D016283:Proto-Oncogene Proteins p21(ras) / Q000097:blood / Q000276:immunology; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000097:blood / Q000276:immunology; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000276:immunology
chemical_list: D017305:Annexin A1; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C000621581:NY-CO16 antigen, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras)