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DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma

Gastric cancer (GC) is the second most widespread cause of cancer-related mortality worldwide. The discovery of novel biomarkers of oncoproteins can facilitate the development of therapeutic strategies for GC treatment. In this study, we identified novel biomarkers by integrating isobaric tags for r...

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Autores principales: Lee, Kam-Fai, Tsai, Ming-Ming, Tsai, Chung-Ying, Huang, Chung-Guei, Ou, Yu-Hsiang, Hsieh, Ching-Chuan, Hsieh, Hsi-Lung, Wang, Chia-Siu, Lin, Kwang-Huei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888682/
https://www.ncbi.nlm.nih.gov/pubmed/31766266
http://dx.doi.org/10.3390/ijms20225689
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author Lee, Kam-Fai
Tsai, Ming-Ming
Tsai, Chung-Ying
Huang, Chung-Guei
Ou, Yu-Hsiang
Hsieh, Ching-Chuan
Hsieh, Hsi-Lung
Wang, Chia-Siu
Lin, Kwang-Huei
author_facet Lee, Kam-Fai
Tsai, Ming-Ming
Tsai, Chung-Ying
Huang, Chung-Guei
Ou, Yu-Hsiang
Hsieh, Ching-Chuan
Hsieh, Hsi-Lung
Wang, Chia-Siu
Lin, Kwang-Huei
author_sort Lee, Kam-Fai
collection PubMed
description Gastric cancer (GC) is the second most widespread cause of cancer-related mortality worldwide. The discovery of novel biomarkers of oncoproteins can facilitate the development of therapeutic strategies for GC treatment. In this study, we identified novel biomarkers by integrating isobaric tags for relative and absolute quantitation (iTRAQ), a human plasma proteome database, and public Oncomine datasets to search for aberrantly expressed oncogene-associated proteins in GC tissues and plasma. One of the most significantly upregulated biomarkers, DEK, was selected and its expression validated. Our immunohistochemistry (IHC) (n = 92) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 72) analyses disclosed a marked increase in DEK expression in tumor tissue, compared with paired nontumor mucosa. Importantly, significantly higher preoperative plasma DEK levels were detected in GC patients than in healthy controls via enzyme-linked immunosorbent assay (ELISA). In clinicopathological analysis, higher expression of DEK in both tissue and plasma was significantly associated with advanced stage and poorer survival outcomes of GC patients. Data from receiver operating characteristic (ROC) curve analysis disclosed a better diagnostic accuracy of plasma DEK than carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), and C-reactive protein (CRP), highlighting its potential as an effective plasma biomarker for GC. Plasma DEK is also more sensitive in tumor detection than the other three biomarkers. Knockdown of DEK resulted in inhibition of GC cell migration via a mechanism involving modulation of matrix metalloproteinase MMP-2/MMP-9 level and vice versa. Our results collectively support plasma DEK as a useful biomarker for making diagnosis and prognosis of GC patients.
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spelling pubmed-68886822019-12-09 DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma Lee, Kam-Fai Tsai, Ming-Ming Tsai, Chung-Ying Huang, Chung-Guei Ou, Yu-Hsiang Hsieh, Ching-Chuan Hsieh, Hsi-Lung Wang, Chia-Siu Lin, Kwang-Huei Int J Mol Sci Article Gastric cancer (GC) is the second most widespread cause of cancer-related mortality worldwide. The discovery of novel biomarkers of oncoproteins can facilitate the development of therapeutic strategies for GC treatment. In this study, we identified novel biomarkers by integrating isobaric tags for relative and absolute quantitation (iTRAQ), a human plasma proteome database, and public Oncomine datasets to search for aberrantly expressed oncogene-associated proteins in GC tissues and plasma. One of the most significantly upregulated biomarkers, DEK, was selected and its expression validated. Our immunohistochemistry (IHC) (n = 92) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 72) analyses disclosed a marked increase in DEK expression in tumor tissue, compared with paired nontumor mucosa. Importantly, significantly higher preoperative plasma DEK levels were detected in GC patients than in healthy controls via enzyme-linked immunosorbent assay (ELISA). In clinicopathological analysis, higher expression of DEK in both tissue and plasma was significantly associated with advanced stage and poorer survival outcomes of GC patients. Data from receiver operating characteristic (ROC) curve analysis disclosed a better diagnostic accuracy of plasma DEK than carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), and C-reactive protein (CRP), highlighting its potential as an effective plasma biomarker for GC. Plasma DEK is also more sensitive in tumor detection than the other three biomarkers. Knockdown of DEK resulted in inhibition of GC cell migration via a mechanism involving modulation of matrix metalloproteinase MMP-2/MMP-9 level and vice versa. Our results collectively support plasma DEK as a useful biomarker for making diagnosis and prognosis of GC patients. MDPI 2019-11-13 /pmc/articles/PMC6888682/ /pubmed/31766266 http://dx.doi.org/10.3390/ijms20225689 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Kam-Fai
Tsai, Ming-Ming
Tsai, Chung-Ying
Huang, Chung-Guei
Ou, Yu-Hsiang
Hsieh, Ching-Chuan
Hsieh, Hsi-Lung
Wang, Chia-Siu
Lin, Kwang-Huei
DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma
title DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma
title_full DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma
title_fullStr DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma
title_full_unstemmed DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma
title_short DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma
title_sort dek is a potential biomarker associated with malignant phenotype in gastric cancer tissues and plasma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888682/
https://www.ncbi.nlm.nih.gov/pubmed/31766266
http://dx.doi.org/10.3390/ijms20225689
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