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Title: CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer
Authors: Roy R.K. 
Hoppe M.M. 
Srivastava S. 
Samanta A. 
Sharma N.
Tan K.T. 
Yang H.
Voon D.C. 
Pang B. 
Teh M. 
Murata-Kamiya N.
Hatakeyama M.
Chang Y.-T. 
Yong W.P. 
Ito Y. 
Ho K.Y. 
Tan P. 
Soong R. 
Koeffler P.H.
Yeoh K.G. 
Jeyasekharan A.D. 
Keywords: biological marker
CagA protein
cancer antibody
carcinoembryonic antigen related cell adhesion molecule 6
bacterial antigen
bacterial protein
cagA protein, Helicobacter pylori
CEACAM6 protein, human
cell adhesion molecule
glycosylphosphatidylinositol anchored protein
leukocyte antigen
tumor marker
bacterium identification
binding affinity
binding site
cancer diagnosis
controlled study
disease activity
gene expression
Helicobacter pylori
human cell
in vitro study
molecular dynamics
molecular pathology
protein binding
protein determination
protein expression
protein function
quantitative analysis
stomach cancer
stomach carcinogenesis
tissue level
tissue microarray
fluorescent antibody technique
Helicobacter infection
stomach tumor
Antigens, Bacterial
Antigens, CD
Bacterial Proteins
Biomarkers, Tumor
Cell Adhesion Molecules
Fluorescent Antibody Technique
GPI-Linked Proteins
Helicobacter Infections
Stomach Neoplasms
Issue Date: 2016
Publisher: Impact Journals LLC
Citation: Roy R.K., Hoppe M.M., Srivastava S., Samanta A., Sharma N., Tan K.T., Yang H., Voon D.C., Pang B., Teh M., Murata-Kamiya N., Hatakeyama M., Chang Y.-T., Yong W.P., Ito Y., Ho K.Y., Tan P., Soong R., Koeffler P.H., Yeoh K.G., Jeyasekharan A.D. (2016). CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer. Oncotarget 7 (34) : 55290-55301. ScholarBank@NUS Repository.
Abstract: Early detection of gastric cancers saves lives, but remains a diagnostic challenge. In this study, we aimed to identify cell-surface biomarkers of early gastric cancer. We hypothesized that a subset of plasma membrane proteins induced by the Helicobacter pylori oncoprotein CagA will be retained in early gastric cancers through non-oncogene addiction. An inducible system for expression of CagA was used to identify differentially upregulated membrane protein transcripts in vitro. The top hits were then analyzed in gene expression datasets comparing transcriptome of gastric cancer with normal tissue, to focus on markers retained in cancer. Among the transcripts enriched upon CagA induction in vitro, a significant elevation of CEACAM6 was noted in gene expression datasets of gastric cancer. We used quantitative digital immunohistochemistry to measure CEACAM6 protein levels in tissue microarrays of gastric cancer. We demonstrate an increase in CEACAM6 in early gastric cancers, when compared to matched normal tissue, with an AUC of 0.83 for diagnostic validity. Finally, we show that a fluorescently conjugated CEACAM6 antibody binds avidly to freshly resected gastric cancer xenograft samples and can be detected by endoscopy in real time. Together, these results suggest that CEACAM6 upregulation is a cell surface response to H. pylori CagA, and is retained in early gastric cancers. They highlight a novel link between CEACAM6 expression and CagA in gastric cancer, and suggest CEACAM6 to be a promising biomarker to aid with the fluorescent endoscopic diagnosis of early neoplastic lesions in the stomach.
Source Title: Oncotarget
ISSN: 19492553
DOI: 10.18632/oncotarget.10528
Appears in Collections:Staff Publications

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