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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Veröffentlicht in:International journal of molecular sciences 2019-11, Vol.20 (22), p.5689
Hauptverfasser: 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
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container_issue 22
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container_title International journal of molecular sciences
container_volume 20
creator 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
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) ( = 92) and quantitative real-time polymerase chain reaction (qRT-PCR) ( = 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.
doi_str_mv 10.3390/ijms20225689
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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) ( = 92) and quantitative real-time polymerase chain reaction (qRT-PCR) ( = 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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20225689</identifier><identifier>PMID: 31766266</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Accuracy ; Acute myeloid leukemia ; Adenocarcinoma ; Aged ; Antigens ; Biomarkers ; Biomarkers, Tumor - analysis ; Bladder cancer ; Breast cancer ; Cancer ; Cell Line, Tumor ; Cell Movement ; Cervical cancer ; Chromosomal Proteins, Non-Histone - analysis ; Chromosomal Proteins, Non-Histone - blood ; Chronic lymphocytic leukemia ; Colon ; Colon cancer ; Datasets ; Female ; Gastric cancer ; Glioma ; Hemopoietic system ; Hepatocellular carcinoma ; Humans ; Leukemia ; Lung cancer ; Lymph nodes ; Lymphatic leukemia ; Lymphatic system ; Lymphocytes T ; Macrophages ; Male ; Medical prognosis ; Medical research ; Melanoma ; Metastases ; Metastasis ; Middle Aged ; Myeloid leukemia ; Neoplasm Metastasis - diagnosis ; Neoplasm Metastasis - pathology ; Oncogene Proteins - analysis ; Oncogene Proteins - blood ; Oral squamous cell carcinoma ; Pancreas ; Peritoneal seeding ; Peritoneum ; Phenotypes ; Poly-ADP-Ribose Binding Proteins - analysis ; Poly-ADP-Ribose Binding Proteins - blood ; Prognosis ; Prostate cancer ; Proteins ; Retina ; Retinoblastoma ; Stomach Neoplasms - blood ; Stomach Neoplasms - diagnosis ; Stomach Neoplasms - pathology ; Survival Analysis ; Tumors ; Urine</subject><ispartof>International journal of molecular sciences, 2019-11, Vol.20 (22), p.5689</ispartof><rights>2019. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). 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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) ( = 92) and quantitative real-time polymerase chain reaction (qRT-PCR) ( = 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). 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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><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-786519df284b39c10558f39ba2c219b0df4161c40aad7ca1b0720b333b95da0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Accuracy</topic><topic>Acute myeloid leukemia</topic><topic>Adenocarcinoma</topic><topic>Aged</topic><topic>Antigens</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Bladder cancer</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cervical cancer</topic><topic>Chromosomal Proteins, Non-Histone - analysis</topic><topic>Chromosomal Proteins, Non-Histone - blood</topic><topic>Chronic lymphocytic leukemia</topic><topic>Colon</topic><topic>Colon cancer</topic><topic>Datasets</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Glioma</topic><topic>Hemopoietic system</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Lung cancer</topic><topic>Lymph nodes</topic><topic>Lymphatic leukemia</topic><topic>Lymphatic system</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Melanoma</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Myeloid leukemia</topic><topic>Neoplasm Metastasis - diagnosis</topic><topic>Neoplasm Metastasis - pathology</topic><topic>Oncogene Proteins - analysis</topic><topic>Oncogene Proteins - blood</topic><topic>Oral squamous cell carcinoma</topic><topic>Pancreas</topic><topic>Peritoneal seeding</topic><topic>Peritoneum</topic><topic>Phenotypes</topic><topic>Poly-ADP-Ribose Binding Proteins - analysis</topic><topic>Poly-ADP-Ribose Binding Proteins - blood</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>Proteins</topic><topic>Retina</topic><topic>Retinoblastoma</topic><topic>Stomach Neoplasms - blood</topic><topic>Stomach Neoplasms - diagnosis</topic><topic>Stomach Neoplasms - pathology</topic><topic>Survival Analysis</topic><topic>Tumors</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Kam-Fai</creatorcontrib><creatorcontrib>Tsai, Ming-Ming</creatorcontrib><creatorcontrib>Tsai, Chung-Ying</creatorcontrib><creatorcontrib>Huang, Chung-Guei</creatorcontrib><creatorcontrib>Ou, Yu-Hsiang</creatorcontrib><creatorcontrib>Hsieh, Ching-Chuan</creatorcontrib><creatorcontrib>Hsieh, Hsi-Lung</creatorcontrib><creatorcontrib>Wang, Chia-Siu</creatorcontrib><creatorcontrib>Lin, Kwang-Huei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; 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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) ( = 92) and quantitative real-time polymerase chain reaction (qRT-PCR) ( = 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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31766266</pmid><doi>10.3390/ijms20225689</doi><orcidid>https://orcid.org/0000-0001-8302-2472</orcidid><orcidid>https://orcid.org/0000-0002-4495-6616</orcidid><orcidid>https://orcid.org/0000-0002-5649-2222</orcidid><oa>free_for_read</oa></addata></record>
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source MEDLINE; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central
subjects Accuracy
Acute myeloid leukemia
Adenocarcinoma
Aged
Antigens
Biomarkers
Biomarkers, Tumor - analysis
Bladder cancer
Breast cancer
Cancer
Cell Line, Tumor
Cell Movement
Cervical cancer
Chromosomal Proteins, Non-Histone - analysis
Chromosomal Proteins, Non-Histone - blood
Chronic lymphocytic leukemia
Colon
Colon cancer
Datasets
Female
Gastric cancer
Glioma
Hemopoietic system
Hepatocellular carcinoma
Humans
Leukemia
Lung cancer
Lymph nodes
Lymphatic leukemia
Lymphatic system
Lymphocytes T
Macrophages
Male
Medical prognosis
Medical research
Melanoma
Metastases
Metastasis
Middle Aged
Myeloid leukemia
Neoplasm Metastasis - diagnosis
Neoplasm Metastasis - pathology
Oncogene Proteins - analysis
Oncogene Proteins - blood
Oral squamous cell carcinoma
Pancreas
Peritoneal seeding
Peritoneum
Phenotypes
Poly-ADP-Ribose Binding Proteins - analysis
Poly-ADP-Ribose Binding Proteins - blood
Prognosis
Prostate cancer
Proteins
Retina
Retinoblastoma
Stomach Neoplasms - blood
Stomach Neoplasms - diagnosis
Stomach Neoplasms - pathology
Survival Analysis
Tumors
Urine
title DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma
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