Dataset Information

Discover the molecular biomarker associated with cell death and extracellular matrix module in ovarian cancer.

ABSTRACT: High throughput technologies have provided many new research methods for ovarian cancer investigation. In tradition, in order to find the underlying functional mechanisms of the survival-associated genes, gene sets enrichment analysis (GSEA) is always regarded as the important choice. However, GSEA produces too many candidate genes and cannot discover the signaling transduction cascades. In this work, we have used a network-based strategy to optimize the discovery of biomarkers using multifactorial data, including patient expression, clinical survival, and protein-protein interaction (PPI) data. The biomarkers discovered by this strategy belong to the network-based biomarker, which is apt to reveal the underlying functional mechanisms of the biomarker. In this work, over 400 expression arrays in ovarian cancer have been analyzed: the results showed that cell death and extracellular module are the main themes related to ovarian cancer progression.

SUBMITTER: Liu Q

PROVIDER: S-EPMC4378326 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Discover the molecular biomarker associated with cell death and extracellular matrix module in ovarian cancer.

Liu Qiang Q Guo Jianxin J Cui Jinghong J Wang Jing J Yi Ping P

BioMed research international 20150316

High throughput technologies have provided many new research methods for ovarian cancer investigation. In tradition, in order to find the underlying functional mechanisms of the survival-associated genes, gene sets enrichment analysis (GSEA) is always regarded as the important choice. However, GSEA produces too many candidate genes and cannot discover the signaling transduction cascades. In this work, we have used a network-based strategy to optimize the discovery of biomarkers using multifactor ...[more]

PMID: 25861644

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Project description:ObjectiveHigh blood flow induces neointimal atrophy in polytetrafluoroethylene (PTFE) aortoiliac grafts and a tight external PTFE wrap of the iliac artery induces medial atrophy. In both nonhuman primate models, atrophy with loss of smooth muscle cells and extracellular matrix (ECM) begins at ≤4 days. We hypothesized that matrix loss would be linked to cell death, but the factors and mechanisms involved are not known. The purpose of this study was to determine commonly regulated genes in these two models, which we hypothesized would be a small set of genes that might be key regulators of vascular atrophy.MethodsDNA microarray analysis (Sentrix Human Ref 8; Illumina, San Diego, Calif; ∼23,000 genes) was performed on arterial tissue from the wrap model (n = 9) and graft neointima from the graft model (n = 5) 1 day after wrapping or the switch to high flow, respectively. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was also performed. Expression of this vascular atrophy gene set was also studied after Fas ligand-induced cell death in cultured smooth muscle cells and organ cultured arteries.ResultsMicroarray analysis showed 15 genes were regulated in the same direction in both atrophy models: 9 upregulated and 6 downregulated. Seven of nine upregulated genes were confirmed by qRT-PCR in both models. Upregulated genes included the ECM-degrading enzymes ADAMTS4, tissue plasminogen activator (PLAT), and hyaluronidase 2; possible growth regulatory factors, including chromosome 8 open reading frame 4 and leucine-rich repeat family containing 8; a differentiation regulatory factor (musculoskeletal embryonic nuclear protein 1); a dead cell removal factor (ficolin 3); and a prostaglandin transporter (solute carrier organic anion transporter family member 2A1). Five downregulated genes were confirmed but only in one or the other model. Of the seven upregulated genes, ADAMTS4, PLAT, hyaluronidase 2, solute carrier organic anion transporter family member 2A1, leucine-rich repeat family containing 8, and chromosome 8 open reading frame 4 were also upregulated in vitro in cultured smooth muscle cells or cultured iliac artery by treatment with FasL, which causes cell death. However, blockade of caspase activity with Z-VAD inhibited FasL-mediated cell death, but not gene induction.ConclusionSeven gene products were upregulated in two distinctly different in vivo nonhuman primate vascular atrophy models. Induction of cell death by FasL in vitro induced six of these genes, including the ECM-degrading factors ADAMTS4, hyaluronidase 2, and PLAT, suggesting a mechanism by which the program of tissue atrophy coordinately removes extracellular matrix as cells die. These genes may be key regulators of vascular atrophy.

Dataset Information

Discover the molecular biomarker associated with cell death and extracellular matrix module in ovarian cancer.

Publications

Discover the molecular biomarker associated with cell death and extracellular matrix module in ovarian cancer.

Similar Datasets

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