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

Abstract

OBJECTIVE:

To discover and confirm blood-based colon cancer early-detection markers.

DESIGN:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Jung-Hyun Rho, Jon J Ladd, Christopher I Li, John D Potter, Yuzheng Zhang, David Shelley, David Shibata, Domenico Coppola, Hiroyuki Yamada, Hidenori Toyoda, Toshifumi Tada, Takashi Kumada, Dean E Brenner, Samir M Hanash, Paul D Lampe
• Journal: Gut (Gut) Vol. 67 Issue 3 Pg. 473-484 (03 2018) ISSN: 1468-3288 [Electronic] England
• PMID: 27821646 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Chemical References

• Adaptor Proteins, Signal Transducing
• BAG4 protein, human
• Biomarkers, Tumor
• CA-19-9 Antigen
• CD44 protein, human
• Hyaluronan Receptors
• IL6ST protein, human
• Lewis X Antigen
• Oligosaccharides
• von Willebrand Factor
• Cytokine Receptor gp130
• ErbB Receptors

Topics

• Adaptor Proteins, Signal Transducing (blood, metabolism)
• Adenoma (blood, diagnosis, metabolism)
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (blood, metabolism)
• CA-19-9 Antigen (metabolism)
• Case-Control Studies
• Colonic Neoplasms (blood, diagnosis, metabolism)
• Cytokine Receptor gp130 (blood, metabolism)
• Early Detection of Cancer (methods)
• ErbB Receptors (blood, metabolism)
• Female
• Humans
• Hyaluronan Receptors (blood, metabolism)
• Lewis X Antigen (metabolism)
• Male
• Middle Aged
• Oligosaccharides (metabolism)
• Protein Array Analysis
• von Willebrand Factor (metabolism)