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Expression Analysis Of Mmps And Their Related Genes Based On The Molecular Interaction Network In Gastric Cancer Tissues

Posted on:2016-10-15Degree:MasterType:Thesis
Country:ChinaCandidate:J T XuFull Text:PDF
GTID:2284330482954646Subject:Pathogen Biology
Abstract/Summary:PDF Full Text Request
Gastric cancer is one of the most common malignant tumor around the world. Overall, gastric cancer is accounts for the fourth of incidence and the second of mortality rates among all cancers in the world. Different kind of risk factors could coordinate to manipulate gene expression or mutation or epigenetic alterations and eventually result in gastric cancer development. Matrix metalloproteinases(MMPs) are a class of endogenous proteolytic enzymes, specifically degrade the basement membrane and extracellular matrix components, participate in angiogenesis, cell proliferation and apoptosis, migration and invasion of cells play an important role in regulation. Studies have shown that, MMPs are closely related to the occurrence of gastric cancer, lung cancer, breast cancer and other malignant tumors. Although the correlation between MMPs and cancer has been widely recognized, but for understanding the mechanism of cancer is still limited. Therefore, through the establishment of human gastric carcinoma MMPs protein interaction networks, systemic and comprehensive analysis of the relationship between gene regulation will be of great significance to explain the molecular pathological mechanism of gastric cancer.The study on gene expression differences through analysis of high-throughput gene microarray of 10 gastric cancer tissues and adjacent normal tissues. For differential expression gene, using Matlab and david database to make clustering analysis and biological function and pathway enrichment analysis respectively. Use the Real Time-PCR experiment of MMPs family in gastric carcinoma and the expression level of mRNA, BioGRID database and STRING database interaction prediction based on MMPs protein family. The combination of database predicted MMPs interaction differentially screening of protein and expression profile chip, interaction network construction of MMPs in gastric cancer family related protein, and analysis of biological function and pathway of key genes in the network.Microarray analysis showed that a total of 1666 gene significantly difference expression in gastric carcinoma, of which 1540 genes up-regulated, 126 genes showed down-regulated of expression. The up-regulated genes were mainly involved in endopeptidase activation, protease activation, metalloendopeptidase activity and extracellular matrix structure pathway. The down-regulated genes were mainly involved in digestion, ion transport, metal ion transport, oxidoreduction, gastric acid secretion pathway. Real Time-PCR experiments further confirmed the gastric carcinoma MMP family gene expression level was significantly higher than that in normal gastric mucosa tissues, and the expression level of the gene chip results are consistent with the gastric carcinoma MMP family gene expression level. The MMP family interaction genes based on BioGRID database and STRING database, and gene chip screening based on constructed in gastric cancer, we create a construction of gastric cancer related MMP family protein interaction network. 18 genes among the genes in gastric cancer and MMP family have close function, mainly involving the extracellular matrix decomposition and ECM- receptor interactions of pathway, which is closely related with tumor invasion and metastasis.In summary, MMP family appeared significantly higher expression in gastric cancer tissue. Through the construction of gastric cancer related MMP family protein interaction networks, revealing the decomposition of cell signal transduction pathway of extracellular matrix of MMPs family in gastric cancer mainly involved in tumor cell. With the in-depth study of the relationship between MMP family and gastric cancer, will contribute to the pathogenesis of tumors and explore a new target for tumor therapy.
Keywords/Search Tags:Matrix metalloproteinase, Gastric cancer, Regulatory network, Microarray
PDF Full Text Request
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