Journal Article

Protein and glycomic plasma markers for early detection of adenoma and colon cancer

Zhang, Yuzheng, Yamada, Hiroyuki, Shelley, David, Shibata, David, Coppola, Domenico, Lampe, Paul D, Li, Christopher I, Potter, John D, Rho, Jung-hyun, Tada, Toshifumi, Hanash, Samir M, Toyoda, Hidenori, Kumada, Takashi, Ladd, Jon J, Brenner, Dean E

2018

Overview

ObjectiveTo discover and confirm blood-based colon cancer early-detection markers.DesignWe created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays.ResultsIn the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and Lewis-X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterised by a range of area under the curves from 0.90 (95% CI 0.82 to 0.98) to 0.86 (95% CI 0.83 to 0.88), for the larger second and fourth sets, respectively.ConclusionsA panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies.

• Publisher: BMJ,BMJ Publishing Group LTD
• Subject: Adaptor Proteins, Signal Transducing / Adaptor Proteins, Signal Transducing - blood / Adaptor Proteins, Signal Transducing - metabolism / Adenoma / Adenoma - blood / Adenoma - diagnosis / Adenoma - metabolism / Adult / Age / Aged / Aged, 80 and over / Antibody microarrays / Antigens / Arrays / Biomarkers / Biomarkers, Tumor / Biomarkers, Tumor - blood / Biomarkers, Tumor - metabolism / Breast cancer / CA-19-9 Antigen / CA-19-9 Antigen - metabolism / Cardiovascular disease / Case-Control Studies / CD44 antigen / Colon cancer / Colonic Neoplasms / Colonic Neoplasms - blood / Colonic Neoplasms - diagnosis / Colonic Neoplasms - metabolism / Colonoscopy / Colorectal cancer / Cytokine Receptor gp130 / Cytokine Receptor gp130 - blood / Cytokine Receptor gp130 - metabolism / Cytokines / Deoxyribonucleic acid / DNA / DNA methylation / Early Detection of Cancer / Early Detection of Cancer - methods / Endoscopy / Epidermal growth factor / Epidermal growth factor receptors / ErbB Receptors / ErbB Receptors - blood / ErbB Receptors - metabolism / FDA approval / Female / Health risk assessment / Humans / Hyaluronan Receptors / Hyaluronan Receptors - blood / Hyaluronan Receptors - metabolism / Immunoblotting / Immunohistochemistry / Interleukin 6 / Lewis X Antigen / Lewis X Antigen - metabolism / Male / Medical prognosis / Medical screening / Middle Aged / Mortality / Oligosaccharides / Oligosaccharides - metabolism / Ovarian cancer / Plasma / Population / Protein Array Analysis / Proteins / Tumors / Von Willebrand factor / von Willebrand Factor - metabolism / Womens health