Evaluation of novel serological markers for early diagnosis of colorectal neoplasia SID 85
Final Report Abstract
Colorectal cancer (CRC) screening by a sensitive blood test would be a highly attractive alternative to colonoscopy. This DFG project aimed to investigate novel serological markers for the early detection of advanced colorectal neoplasm (CRC and advanced adenomas) in the target population of CRC screening. Furthermore, a biobank with samples for future research should be established. We successfully recruited about 2000 study participants (men and women aged 54 to 75 that underwent screening colonoscopy) and collected a large quantity of blood and stool samples to enable current and future assessments of many promising putative biomarkers in the target population of CRC screening. Due to insurmountable difficulties in the establishment of the immunoassays for colon cancer-specific antigens 2, 3 and 4, we had to discard the initial plan to measure these biomarkers. Instead we performed autoantibody measurements by a fluorescent bead-based glutathione S-transferase capture immunosorbent assay in all newly recruited participants. Furthermore, we invested in doing analyses and writing publications on potential blood markers and diagnostic tests that had been measured/conducted in samples from BliTz participants recruited before the initiation of this DFG project. Thus we gained a large insight which biomarkers might have the potential to be useful for CRC screening and which biomarkers don’t. In contrast to the fecal immunochemical tests, none of the blood-based biomarkers reached sufficient sensitivity and specificity to be used for CRC screening alone. However, some autoantibodies, micro-RNAs and protein biomarkers seem to be useful for CRC screening when being combined in multi-marker panels.
Publications
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(2012). Comparison and combination of blood-based inflammatory markers with faecal occult blood tests for non-invasive colorectal cancer screening. Br J Cancer 106: 1424-30
Tao S, Haug U, Kuhn K, Brenner H
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(2013). Comparative evaluation of nine faecal immunochemical tests for the detection of colorectal cancer. Acta Oncol 52: 1667-75
Tao S, Seiler CM, Ronellenfitsch U, Brenner H
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(2013). Identification and evaluation of plasma MicroRNAs for early detection of colorectal cancer. PLoS One 8: e62880
Luo X, Stock C, Burwinkel B, Brenner H
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(2013). Matching of controls may lead to biased estimates of specificity in the evaluation of cancer screening tests. J Clin Epidemiol 66: 202-8
Brenner H, Altenhofen L, Tao S
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(2013). Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy. Eur J Cancer 49: 3049-54
Brenner H, Tao S
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(2013). Well adjusted qualitative immunochemical faecal occult blood tests could be a promising alternative for inexpensive, high-quality colorectal cancer screening. Eur J Cancer Prev 22: 305-10
Tao S, Brenner H
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(2015). Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting. Clin Cancer Res 21: 3318-26
Chen H, Zucknick M, Werner S, Knebel P, Brenner H
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(2016). Empirical evaluation demonstrated importance of validating biomarkers for early detection of cancer in screening settings to limit the number of false positive findings. J Clin Epidemiol.
Chen H, Knebel P, Brenner H
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(2016). Evaluation of the diagnostic value of 64 simultaneously measured autoantibodies for early detection of gastric cancer. Sci Rep 6: 25467
Werner S, Chen H, Butt J, Michel A, Knebel P, Holleczek B, Zornig I, Eichmuller SB, Jager D, Pawlita M, Waterboer T, Brenner H
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(2016). Prospective evaluation of 64 serum autoantibodies as biomarkers for early detection of colorectal cancer in a true screening setting. Oncotarget
Chen H, Werner S, Butt J, Zornig I, Knebel P, Michel A, Eichmuller SB, Jager D, Waterboer T, Pawlita M, Brenner H
