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

Abstract

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.

Long Noncoding RNA NR2F1-AS1 Enhances the Migration and Invasion of Hepatocellular Carcinoma via Modulating miR-642a/DEK Pathway

“…DEK is a potential biomarker and oncogene, which is reported in many cancers [25][26][27]. DEK was found to involve in the development of pancreatic cancer as a target of miR-200a [28].…”

DEK‐targeting aptamer DTA‐64 attenuates bronchial EMT‐mediated airway remodelling by suppressing TGF‐β1/Smad, MAPK and PI3K signalling pathway in asthma

“…DEK also promoted the proliferation and invasion of lung cancer cells A549 and H1299 through β‐catenin and Wnt signalling pathways 6 . Silencing of DEK resulted in the inhibition of gastric cancer cell migration through the matrix metalloproteinase (MMP‐2/ MMP‐9) pathways 7 . Besides, recombinant DEK promoted the proliferation of mouse hematopoietic stem cells, which was related to the enhanced activation of extracellular signal‐regulated kinases (ERK1/2), p38 mitogen‐activated protein kinases (p38 MAPK) and AKT signalling pathways 8,9 .…”

Anticancer Effects of Helminthostachys zeylanica Ethyl acetate Extracts on Human Gastric Cancer Cells through Downregulation of the TNF-α-activated COX-2-cPLA2-PGE2 Pathway

“…Chen and Dr. D.W. Zhou, Xiamen University, Fujian, China. All cells were cultured in RPMI 1640 medium (Invitrogen, Carlsbad, CA, USA) containing 10% fetal bovine serum (FBS) plus 100 IU/mL penicillin G, 100 mg/mL streptomycin sulfate (Sigma-Aldrich, St Louis, MO, USA), and nonessential amino acids at 37 °C in 95% air and 5% CO 2 as described previously 40 . The cells were either left untreated or were treated with H. zeylanica -E2 and/or TNF-α.…”

“…The cells were treated with H. zeylanica- E1 (0, 10, 50, 100, 500, 1,000, 5000, or 10 000 μg/mL) or H. zeylanica -E2 (0, 1, 5, 10, 20, 40, 80, or 100 μg/mL) 39 for 24 or 48 h. Next, 0.25 mg/mL MTT reagent (Bio-Rad Laboratories, Hercules, CA, USA) was added (100 μL/well), the incubation was continued for 0.5 h, and 100 μL of dimethyl sulfoxide was then added to the medium. The optical density at 570 nm was detected using a microplate reader (SpectraMax i3; Kelowna International Scientific Inc., CA, USA) as described previously 36 , 40 .…”

“…PGE 2 protein level in the medium from cells treated with H. zeylanica- E2 or CLC for 0, 24, or 48 h was measured using a human protein PGE 2 enzyme immunoassay kit (Enzo Life Sciences, Farmingdale, NY, USA). Fluorescence intensity was measured at 450 nm using a SpectraMax i3 microplate reader (Kelowna International Scientific Inc.) 40 , 45 .…”