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

被引:16
|
作者
Lee, Kam-Fai [1 ]
Tsai, Ming-Ming [2 ,3 ,4 ]
Tsai, Chung-Ying [5 ,6 ,7 ]
Huang, Chung-Guei [8 ,9 ,10 ]
Ou, Yu-Hsiang [5 ,10 ]
Hsieh, Ching-Chuan [4 ]
Hsieh, Hsi-Lung [2 ,3 ,11 ]
Wang, Chia-Siu [4 ]
Lin, Kwang-Huei [3 ,5 ,12 ]
机构
[1] Chang Gung Mem Hosp, Dept Pathol, Chiayi 613, Taiwan
[2] Chang Gung Univ Sci & Technol, Div Basic Med Sci, Dept Nursing, Taoyuan 333, Taiwan
[3] Chang Gung Univ Sci & Technol, Coll Human Ecol, Res Ctr Chinese Herbal Med, Taoyuan 333, Taiwan
[4] Chang Gung Mem Hosp, Dept Gen Surg, Chiayi 613, Taiwan
[5] Chang Gung Univ, Coll Med, Dept Biochem, Taoyuan 333, Taiwan
[6] Chang Gung Mem Hosp, Kidney Res Ctr, Taoyuan 333, Taiwan
[7] Chang Gung Mem Hosp, Dept Nephrol, Taoyuan 333, Taiwan
[8] Chang Gung Univ, Dept Med Biotechnol & Lab Sci, Taoyuan 333, Taiwan
[9] Chang Gung Univ, Grad Inst Biomed Sci, Taoyuan 333, Taiwan
[10] Chang Gung Mem Hosp, Dept Lab Med, Taoyuan 333, Taiwan
[11] Chang Gung Mem Hosp, Dept Neurol, Taoyuan 333, Taiwan
[12] Chang Gung Mem Hosp, Liver Res Ctr, Taoyuan 333, Taiwan
关键词
DEK; biomarker; gastric cancer; metastasis; prognosis; diagnosis; CELL-GROWTH; APOPTOSIS; CARCINOMA; ONCOGENE; OVEREXPRESSION; AUTOANTIBODIES; PROLIFERATION; ONCOPROTEIN; METASTASIS; ARTHRITIS;
D O I
10.3390/ijms20225689
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:19
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