Protein and glycomic plasma markers for early detection of adenoma and colon cancer.
To discover and confirm blood-based colon cancer early-detection markers.



We 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.



In 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.



A 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.
Translational Research Program, Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Jung-Hyun
JH
Rho
Translational Research Program, Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Jon J
JJ
Ladd
Translational Research Program, Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Christopher I
CI
Li
Translational Research Program, Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|School of Public Health, University of Washington, Seattle, Washington, USA17.|Centre for Public Health Research, Massey University, Wellington, New Zealand.
John D
JD
Potter
Translational Research Program, Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Yuzheng
Y
Zhang
Translational Research Program, Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
David
D
Shelley
University of Tennessee Health Science Center, Memphis, Tennessee, USA.
David
D
Shibata
Moffitt Cancer Center, Tampa, Florida, USA.
Domenico
D
Coppola
Wako Life Sciences, Inc., Mountain View, California, USA.
Hiroyuki
H
Yamada
Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan.
Hidenori
H
Toyoda
Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan.
Toshifumi
T
Tada
Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan.
Takashi
T
Kumada
Great Lakes New England (GLNE) Clinical Validation Center of EDRN, University of Michigan Medical Center, Ann Arbor, Michigan, USA.|VA Medical Center, Ann Arbor, Michigan, USA.
Dean E
DE
Brenner
Department of Clinical Cancer Prevention, Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Samir M
SM
Hanash
Translational Research Program, Public Health Sciences Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Paul D
PD
Lampe
D048868:Adaptor Proteins, Signal Transducing / Q000097:blood / Q000378:metabolism; D000236:Adenoma / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D018395:CA-19-9 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000097:blood / Q000378:metabolism; D055088:Early Detection of Cancer / Q000379:methods*; D066246:ErbB Receptors / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000097:blood / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009844:Oligosaccharides / Q000378:metabolism; D040081:Protein Array Analysis; D014841:von Willebrand Factor / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C116906:BAG4 protein, human; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C494199:IL6ST protein, human; D016256:Lewis X Antigen; D009844:Oligosaccharides; D014841:von Willebrand Factor; D050822:Cytokine Receptor gp130; D066246:ErbB Receptors
COLORECTAL ADENOMAS; COLORECTAL CANCER; COLORECTAL CANCER SCREENING; TUMOUR MARKERS