Unknown,Transcriptomics,Genomics,Proteomics

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Characterization of differentially expressed genes involved in pathways associated with gastric cancer

ABSTRACT: To explore the patterns of gene expression in gastric cancer, a total of 32 paired gastric cancer and noncancerous tissues from patients were collected for gene expression microarray analyses. Limma methods were applied to analyze the data, and genes were considered to be significantly differentially expressed if the False Discovery Rate (FDR) values < 0.01, P-value < 0.01 and the fold change >2. Subsequently, Gene Ontology (GO) analysis was used to analyze the main functions of the differentially expressed genes. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we found pathways significantly associated with the differential genes. Gene-Act network and Co-Expression networks were built respectively based on the relationships among the genes, proteins and compounds in the database. There were 2371 differential mRNAs and 350 differential lncRNAs in our microarray data. The GO categories, pathway analyses and the Gene-Act network showed a consistent result that up-regulated genes were involved in tumorigenesis, migration, angiogenesis and microenvironment formation, while down-regulated genes were involved in metabolism. The results of this study provide some novel findings on genes, pathways and the co-expression network in gastric cancer which will be useful to guide further investigation and target therapy for this disease. 32 gastric cancer tissues and 32 paired noncancerous tissues were collected for this microarray analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: hao li

PROVIDER: E-GEOD-65801 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Purpose: We aimed to investigate the effect of several anti-leukemia drugs in combination with decitabine (DAC) on the proliferation of myeloid leukemia cells in vitro and in vivo, to select the most efficient combination group and explore associated mechanisms of these combination therapies. Experimental Design: After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway. Results: The sequential combination of DAC and IDA showed synergistic induction of cell death in U937, HEL, SKM-1 and cells isolated from AML patients. Importantly, the inhibition of tumor growth in the sequential combination group was found to be significantly higher than that of single drug group or control group in vivo. Moreover, sequential treatment with DAC and IDA induced apoptosis and depression of the Wnt/β-catenin pathway in both culture and animal studies. Conclusions: Our findings showed that sequentially combining decitabine with idarubicin had a synergistic anti-leukemia effect. These findings were attributed to demethylation of Wnt pathway inhibitors and downregulation of Wnt pathway nuclear targets observed in vitro and in vivo. After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway.

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Characterization of differentially expressed genes involved in pathways associated with gastric cancer

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