Human blood autoantibodies in the detection of colorectal cancer

Negm, Ola H.; Hamed, Mohamed R.; Schoen, Robert E.; Whelan, Richard L.; Steele, Robert J.; Scholefield, John; Dilnot, Elizabeth M.; Shantha Kumara, H.M.C.; Robertson, John F.R.; Sewell, Herbert F.

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 interpo- lated 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;stageI(n=19),stageII(n=40),stageIII(n=34)andstageIV(n=6)wassimilar (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.

Citation

Negm, O. H., Hamed, M. R., Schoen, R. E., Whelan, R. L., Steele, R. J., Scholefield, J., …Sewell, H. F. (2016). Human blood autoantibodies in the detection of colorectal cancer. PLoS ONE, 11(7), 1-14. https://doi.org/10.1371/journal.pone.0156971

• Journal Article Type: Article
• Acceptance Date: May 23, 2016
• Online Publication Date: Jul 6, 2016
• Publication Date: Jul 6, 2016
• Deposit Date: Jul 18, 2017
• Publicly Available Date: Jul 18, 2017
• Journal: PLoS ONE
• Electronic ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 7
• Article Number: e0156971
• Pages: 1-14
• DOI: https://doi.org/10.1371/journal.pone.0156971
• Public URL: https://nottingham-repository.worktribe.com/output/802068
• Additional Information: Negm OH, Hamed MR, Schoen RE,; Whelan RL, Steele RJ, Scholefield J, et al. (2016); Human Blood Autoantibodies in the Detection of; Colorectal Cancer. PLoS ONE 11(7): e0156971.; doi:10.1371/journal.pone.0156971
• Contract Date: Jul 18, 2017