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CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer

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 e...

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Autores principales: Roy, Rony K., Hoppe, Michal M., Srivastava, Supriya, Samanta, Animesh, Sharma, Neel, Tan, Kar Tong, Yang, Henry, Voon, Dominic C., Pang, Brendan, Teh, Ming, Murata-Kamiya, Naoko, Hatakeyama, Masanori, Chang, Young-Tae, Yong, Wei Peng, Ito, Yoshiaki, Ho, Khek Yu, Tan, Patrick, Soong, Richie, Koeffler, Phillip H., Yeoh, Khay Guan, Jeyasekharan, Anand D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342417/
https://www.ncbi.nlm.nih.gov/pubmed/27421133
http://dx.doi.org/10.18632/oncotarget.10528
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author Roy, Rony K.
Hoppe, Michal M.
Srivastava, Supriya
Samanta, Animesh
Sharma, Neel
Tan, Kar Tong
Yang, Henry
Voon, Dominic C.
Pang, Brendan
Teh, Ming
Murata-Kamiya, Naoko
Hatakeyama, Masanori
Chang, Young-Tae
Yong, Wei Peng
Ito, Yoshiaki
Ho, Khek Yu
Tan, Patrick
Soong, Richie
Koeffler, Phillip H.
Yeoh, Khay Guan
Jeyasekharan, Anand D.
author_facet Roy, Rony K.
Hoppe, Michal M.
Srivastava, Supriya
Samanta, Animesh
Sharma, Neel
Tan, Kar Tong
Yang, Henry
Voon, Dominic C.
Pang, Brendan
Teh, Ming
Murata-Kamiya, Naoko
Hatakeyama, Masanori
Chang, Young-Tae
Yong, Wei Peng
Ito, Yoshiaki
Ho, Khek Yu
Tan, Patrick
Soong, Richie
Koeffler, Phillip H.
Yeoh, Khay Guan
Jeyasekharan, Anand D.
author_sort Roy, Rony K.
collection PubMed
description 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.
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spelling pubmed-53424172017-03-22 CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer Roy, Rony K. Hoppe, Michal M. Srivastava, Supriya Samanta, Animesh Sharma, Neel Tan, Kar Tong Yang, Henry Voon, Dominic C. Pang, Brendan Teh, Ming Murata-Kamiya, Naoko Hatakeyama, Masanori Chang, Young-Tae Yong, Wei Peng Ito, Yoshiaki Ho, Khek Yu Tan, Patrick Soong, Richie Koeffler, Phillip H. Yeoh, Khay Guan Jeyasekharan, Anand D. Oncotarget Research Paper 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. Impact Journals LLC 2016-07-11 /pmc/articles/PMC5342417/ /pubmed/27421133 http://dx.doi.org/10.18632/oncotarget.10528 Text en Copyright: © 2016 Roy et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Roy, Rony K.
Hoppe, Michal M.
Srivastava, Supriya
Samanta, Animesh
Sharma, Neel
Tan, Kar Tong
Yang, Henry
Voon, Dominic C.
Pang, Brendan
Teh, Ming
Murata-Kamiya, Naoko
Hatakeyama, Masanori
Chang, Young-Tae
Yong, Wei Peng
Ito, Yoshiaki
Ho, Khek Yu
Tan, Patrick
Soong, Richie
Koeffler, Phillip H.
Yeoh, Khay Guan
Jeyasekharan, Anand D.
CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer
title CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer
title_full CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer
title_fullStr CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer
title_full_unstemmed CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer
title_short CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer
title_sort ceacam6 is upregulated by helicobacter pylori caga and is a biomarker for early gastric cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342417/
https://www.ncbi.nlm.nih.gov/pubmed/27421133
http://dx.doi.org/10.18632/oncotarget.10528
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