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

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 <3years 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.

Original languageEnglish (US)
Pages (from-to)473-484
Number of pages12
JournalGut
Volume67
Issue number3
DOIs
StatePublished - Mar 1 2018

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Glycomics
Cytokine Receptor gp130
Early Detection of Cancer
Adenoma
Colonic Neoplasms
Blood Proteins
Epidermal Growth Factor Receptor
von Willebrand Factor
Neoplasms
Proteins
Immunohistochemistry
Molecular Chaperones
Immunoblotting
Area Under Curve
Glycoproteins
Antibodies

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Rho, J. H., Ladd, J. J., Li, C. I., Potter, J. D., Zhang, Y., Shelley, D., ... Lampe, P. D. (2018). Protein and glycomic plasma markers for early detection of adenoma and colon cancer. Gut, 67(3), 473-484. https://doi.org/10.1136/gutjnl-2016-312794

Protein and glycomic plasma markers for early detection of adenoma and colon cancer. / Rho, Jung Hyun; Ladd, Jon J.; Li, Christopher I.; Potter, John D.; Zhang, Yuzheng; Shelley, David; Shibata, David; Coppola, Domenico; Yamada, Hiroyuki; Toyoda, Hidenori; Tada, Toshifumi; Kumada, Takashi; Brenner, Dean E.; Hanash, Samir M.; Lampe, Paul D.

In: Gut, Vol. 67, No. 3, 01.03.2018, p. 473-484.

Research output: Contribution to journalArticle

Rho, JH, Ladd, JJ, Li, CI, Potter, JD, Zhang, Y, Shelley, D, Shibata, D, Coppola, D, Yamada, H, Toyoda, H, Tada, T, Kumada, T, Brenner, DE, Hanash, SM & Lampe, PD 2018, 'Protein and glycomic plasma markers for early detection of adenoma and colon cancer', Gut, vol. 67, no. 3, pp. 473-484. https://doi.org/10.1136/gutjnl-2016-312794
Rho JH, Ladd JJ, Li CI, Potter JD, Zhang Y, Shelley D et al. Protein and glycomic plasma markers for early detection of adenoma and colon cancer. Gut. 2018 Mar 1;67(3):473-484. https://doi.org/10.1136/gutjnl-2016-312794
Rho, Jung Hyun ; Ladd, Jon J. ; Li, Christopher I. ; Potter, John D. ; Zhang, Yuzheng ; Shelley, David ; Shibata, David ; Coppola, Domenico ; Yamada, Hiroyuki ; Toyoda, Hidenori ; Tada, Toshifumi ; Kumada, Takashi ; Brenner, Dean E. ; Hanash, Samir M. ; Lampe, Paul D. / Protein and glycomic plasma markers for early detection of adenoma and colon cancer. In: Gut. 2018 ; Vol. 67, No. 3. pp. 473-484.
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AU - Zhang, Yuzheng

AU - Shelley, David

AU - Shibata, David

AU - Coppola, Domenico

AU - Yamada, Hiroyuki

AU - Toyoda, Hidenori

AU - Tada, Toshifumi

AU - Kumada, Takashi

AU - Brenner, Dean E.

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