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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.

SUBMITTER: Lee KF

PROVIDER: S-EPMC6888682 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Lee Kam-Fai KF Tsai Ming-Ming MM Tsai Chung-Ying CY Huang Chung-Guei CG Ou Yu-Hsiang YH Hsieh Ching-Chuan CC Hsieh Hsi-Lung HL Wang Chia-Siu CS Lin Kwang-Huei KH

International journal of molecular sciences 20191113 22

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 ...[more]

PMID: 31766266

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Project description:ObjectiveMicroRNA (miR)-421 plays a key role in cancer progression. It has been reported that circulating miR-421may be a potential tumor marker for the diagnosis of several cancers. However, the role of miR-421 in plasma as a potential biomarker in the diagnosis of precancerous gastric lesions (Pre) and early-stage gastric cancer (GC) remains poorly understood. In this study, we investigated miR-421 in plasma as a novel potential biomarker for the detection of precancerous gastric lesions and early-stage (GC).Materials & methodsThe miRNA content was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-421 content in all subjects was normalized by endogenous miRNA (miR-16). The diagnostic value of miR-421 for Pre and GC was assessed by comparing receiver operating characteristic (ROC) analysis with traditional tumor markers, including CEA, CA125, CA153, CA211 and CA50. The correlation between the expression of miR-421 and the pathological characteristics of Pre and GC was analyzed.ResultsElevated expression of miR-421 in plasma can robustly distinguish the normal population from Pre and GC cases, especially in the early stages of gastric cancer cases (all p < 0.05). The ROC analyses showed that the area under the ROC curve (AUC), sensitivity, accuracy and Youden index of miR-421 were superior to traditional tumor markers (CEA, CA125, CA153, CA211, and CA50) in GC diagnosis, while its specificity was higher than CEA, CA153 and CA50 (all p < 0.05). MiR-421 in plasma had higher AUC value than AFP, CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05), while specificity, accuracy and Youden index of miR-421 was only lower than CA211. The efficiency of miR-421 in the diagnosis of GC was significantly higher than that of CA211 and CA50, and it was significantly higher than CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05). In addition, up-regulation of miR-421 occurred initially in precancerous gastric lesions as well as in the early stage of GC.ConclusionsOverexpression of plasma miR-421 is a novel biomarker for the detection of precancerous lesions and early gastric cancer.

Project description:BackgroundCancer-associated fibroblasts (CAFs) play important roles in tumor progression. However, the behaviors of activated CAFs in gastric cancer remain to be determined. The aim of the present study was to investigate the correlations between activated gastric CAFs and the prognosis of patients with gastric cancer, and to determine the effects of activated CAFs on the malignant phenotype and 5-fluorouracil resistance in this cancer.MethodsNinety-five patients with primary gastric cancer were enrolled in this study. Activation states of gastric CAFs were evaluated by immunohistochemistry. A modified method for the primary culture of gastric CAFs was employed. Types of CAFs and activation states were identified by immunocytochemical and immunofluorescent staining. Cell co-culture and gastric CAF conditioned medium transfer models were established to investigate the paracrine effects of activated CAFs on the migration and invasion of gastric cell lines. The half maximal inhibitory concentration of 5-fluorouracil and levels of cell apoptosis were examined using cell viability assay and flow cytometry, respectively. Protein expression levels of associated molecules were measured by Western blotting.ResultsKaplan-Meier survival curves showed that activated gastric CAFs identified via fibroblast activation protein were significantly related to poorer cumulative survival in gastric cancer patients. Five strains of CAFs were successfully cultured via the modified culture method, and three gastric CAFs strains were identified as activated gastric CAFs. The migration and invasion abilities of gastric cells were significantly enhanced in both the co-culture group and the conditioned medium group. The half maximal inhibitory concentration for 5-fluorouracil in BGC-823 cells was elevated after treatment with conditioned medium, and early apoptosis was inhibited. Additionally, an obvious elevation of epithelial-mesenchymal transition level was observed in the conditioned medium group.ConclusionsActivated gastric CAFs correlate with a poor prognosis of cancer patients and may contribute to the malignant phenotype and the development of resistance to 5-fluorouracil via paracrine action in gastric cancer. Gastric CAFs with a specific activation state might be used as a tumor biomarker within the microenvironment for prognosis and as a new therapeutic target for chemoresistant gastric cancer.

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Project description:The link between microbiota and gastric cancer (GC) has attracted widespread attention. However, the phylogenetic profiles of niche-specific microbiota in the tumor microenvironment is still unclear. Here, mucosa-associated microorganisms from 62 pairs of matched GC tissues and adjacent non-cancerous tissues were characterized by 16S rRNA gene sequencing. Functional profiles of the microbiota were predicted using PICRUSt, and a co-occurrence network was constructed to analyze interactions among gastric microbiota. Results demonstrated that mucosa-associated microbiota from cancerous and non-cancerous tissues established micro-ecological systems that differed in composition, structure, interaction networks, and functions. Microbial richness and diversity were increased in cancerous tissues, with the co-occurrence network exhibiting greater complexity compared with that in non-cancerous tissue. The bacterial taxa enriched in the cancer samples were predominantly represented by oral bacteria (such as Peptostreptococcus, Streptococcus, and Fusobacterium), while lactic acid-producing bacteria (such as Lactococcus lactis and Lactobacillus brevis) were more abundant in adjacent non-tumor tissues. Colonization by Helicobacter pylori, which is a GC risk factor, also impacted the structure of the microbiota. Enhanced bacterial purine metabolism, carbohydrate metabolism and denitrification functions were predicted in the cancer associated microbial communities, which was consistent with the increased energy metabolism and concentration of nitrogen-containing compounds in the tumor microenvironment. Furthermore, the microbial co-occurrence networks in cancerous and non-cancerous tissues of GC patients were described for the first time. And differential taxa and functions between the two groups were identified. Changes in the abundance of certain bacterial taxa, especially oral microbiota, may play a role in the maintenance of the local microenvironment, which is associated with the development or progression of GC.

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

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

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