Prospective evaluation of 64 serum autoantibodies as biomarkers for early detection of colorectal cancer in a true screening setting
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Hongda Chen1, Simone Werner1, Julia Butt2, Inka Zörnig3, Phillip Knebel4, Angelika Michel2, Stefan B. Eichmüller5, Dirk Jäger3, Tim Waterboer2, Michael Pawlita2, Hermann Brenner1,6,7
1Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
2Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DKFZ), Heidelberg, Germany
3Department of Medical Oncology, National Center for Tumor Diseases (NCT), Internal Medicine VI, University of Heidelberg, Heidelberg, Germany
4Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
5GMP & T cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
6Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
7German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Hermann Brenner, e-mail: email@example.com
Keywords: autoantibody, diagnosis, colorectal cancer, tumor-associated antigens, screening setting
Received: November 04, 2015 Accepted: February 05, 2016 Published: February 19, 2016
Novel blood-based screening tests are strongly desirable for early detection of colorectal cancer (CRC). We aimed to identify and evaluate autoantibodies against tumor-associated antigens as biomarkers for early detection of CRC. 380 clinically identified CRC patients and samples of participants with selected findings from a cohort of screening colonoscopy participants in 2005−2013 (N=6826) were included in this analysis. Sixty-four serum autoantibody markers were measured by multiplex bead-based serological assays. A two-step approach with selection of biomarkers in a training set, and validation of findings in a validation set, the latter exclusively including participants from the screening setting, was applied. Anti-MAGEA4 exhibited the highest sensitivity for detecting early stage CRC and advanced adenoma. Multi-marker combinations substantially increased sensitivity at the price of a moderate loss of specificity. Anti-TP53, anti-IMPDH2, anti-MDM2 and anti-MAGEA4 were consistently included in the best-performing 4-, 5-, and 6-marker combinations. This four-marker panel yielded a sensitivity of 26% (95% CI, 13−45%) for early stage CRC at a specificity of 90% (95% CI, 83−94%) in the validation set. Notably, it also detected 20% (95% CI, 13−29%) of advanced adenomas. Taken together, the identified biomarkers could contribute to the development of a useful multi-marker blood-based test for CRC early detection.
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