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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.

Authors

Ola H. Negm ola.negm@nottingham.ac.uk

Mohamed R. Hamed

Robert E. Schoen

Richard L. Whelan

Robert J. Steele

John Scholefield

Elizabeth M. Dilnot

H.M.C. Shantha Kumara

John F.R. Robertson

Herbert F. Sewell



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.

Journal Article Type Article
Publication Date Jul 6, 2016
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 11
Issue 7
Article Number e0156971
APA6 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), https://doi.org/10.1371/journal.pone.0156971
DOI https://doi.org/10.1371/journal.pone.0156971
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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