Gene expression in hypoxic non-small cell lung cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30979 | GEO | 2011/07/28
SECONDARY ACCESSION(S): PRJNA146187
REPOSITORIES: GEO
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Project description:Hypoxia triggers aggressive cancer growth and contributes to chemotherapy resistance. Novel therapeutic strategies aim at targeting hypoxia activated signaling pathways. Tumor hypoxia not only affects neoplastic tumor cells but also the surrounding stroma cells. Therefore, a novel ex vivo model was established, which allows the study of hypoxia effects in fragments of non-small cell lung cancer (NSCLC) with preserved tumor microenvironment and 3D-structure. Microarray analysis identified 107 significantly regulated genes with at least two-fold expression change in hypoxic compared to normoxic fragments. However, only four genes were significantly regulated in both subtypes, adenocarcinoma and squamous cell carcinoma. The hypoxic regulation of these four genes was verified in an independent set using quantitative PCR. Non-small cell lung cancer (NSCLC) fragments were cultured ex vivo under hypoxia or normoxia for three days. cDNA microarray analysis was performed in hypoxic and normoxic lung cancer fragments from ten patients.
2011-07-27 | E-GEOD-30979 | biostudies-arrayexpress
Project description:In vivo profiling of hypoxic gene expression in gliomas using the hypoxia marker EF5 and laser-capture microdissection We have employed the hypoxia marker EF5 coupled with laser capture microdissection to isolate RNA from viable hypoxic and normoxic regions of 9L experimental gliomas. We report the identification of the hypoxic gene expression profile in a solid tumor using a prototypical hypoxia marker EF5, Laser Capture Microdissection (LCM) and Microarray Gene Expression Profiling (EF5-LCM-MGEP). We have utilized LCM to isolate total RNA from normoxic and hypoxic regions in the rat 9L glioma tumor model grown in its isogenic host (Fischer rat). Microarray analysis of the isolated RNA generated an in vivo hypoxia expression profile. For comparison, we also analyzed RNA samples isolated from rat 9L glioma cells in culture exposed to hypoxia or normoxia.
2011-01-13 | E-GEOD-25980 | biostudies-arrayexpress
Project description:Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques. Our main goal is to define a robust hypoxia gene signature in neuroblastoma cell lines. A set of 11 neuroblastoma cell lines were cultured under normoxic and hypoxic conditions for 18 hours, and their gene expression profiles were measured with Affymetrix GeneChip HG-U133 Plus 2.0. We used the l1-l2 regularization framework in order to select the significant probesets defining hypoxic versus normoxic cell lines.
2009-09-30 | GSE17714 | GEO
Project description:Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques. Our main goal is to define a robust hypoxia gene signature in neuroblastoma cell lines. A set of 11 neuroblastoma cell lines were cultured under normoxic and hypoxic conditions for 18 hours, and their gene expression profiles were measured with Affymetrix GeneChip HG-U133 Plus 2.0. We used the l1-l2 regularization framework in order to select the significant probesets defining hypoxic versus normoxic cell lines. Experiment Overall Design: The expression profiles of 11 neuroblastoma cell lines under normoxia vs hypoxia were studied.
2009-10-10 | E-GEOD-17714 | biostudies-arrayexpress
Project description:The Hypoxia-Inducible Factors induce the expression of the histone demethylases JMJD1A (KDM3A) and JMJD2B (KDM4B), linking the hypoxic tumor microenvironment to epigenetic mechanisms that may foster tumor progression. Using transcript profiling, we have identified genes that are regulated by JMJD1A and JMJD2B in both normoxic and hypoxic conditions in SKOV3ip.1 ovarian cancer cells. This dataset includes expression data obtained from exposing ovarian cancer cells to hypoxia in combination with siRNA-mediated knockdown of the hypoxia-inducible histone demethylases JMJD1A and JMJD2B. These data were used to both identify functional overlap between each histone demethylase, as well as identify effectors of tumor growth mediated by JMJD2B (KDM4B) in normoxia and hypoxia.
2017-03-13 | GSE66894 | GEO
Project description:In vivo profiling of hypoxic gene expression in gliomas using the hypoxia marker EF5 and laser-capture microdissection We have employed the hypoxia marker EF5 coupled with laser capture microdissection to isolate RNA from viable hypoxic and normoxic regions of 9L experimental gliomas.
2011-01-13 | GSE25980 | GEO
Project description:Hypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques. Our main goal is to define a robust hypoxia gene signature in neuroblastoma cell lines. A set of 9 neuroblastoma cell lines were cultured under normoxic and hypoxic conditions for 18 hours, and their gene expression profiles were measured with Affymetrix GeneChip HG-U133 Plus 2.0. The clustering analysis of the expression profiles based on different clustering methods consistently revealed that hypoxia was not the major factor characterizing the data set. T-test analysis with multiple testing correction fails to identify significantly differentially expressed genes. Conversely the l1-l2 regularization selects 11 significant probesets while building an effective classification rule. The algorithm is cast within a cross-validation framework in order to achieve an unbiased analysis. The estimated cross-validation error is 17% (3 out of 18). We show that the use of l1-l2 regularization allowed us to model the effect of hypoxia, which was not detected by conventional t-test based approaches and we find a panel of genes able to properly discriminate the normoxic versus the hypoxic status of neuroblastoma cell lines. Experiment Overall Design: The expression profile of 9 neuroblastoma cell lines under normoxia vs hypoxia was studied
2009-04-24 | E-GEOD-15583 | biostudies-arrayexpress
Project description:Hypoxia, a condition of low oxygenation frequently found in triple-negative breast tumors, is often related to increased extracellular vesicle (EV) secretion and favors cell invasion, which is a crucial step for metastasis. Cell invasion is a complex process in which cell morphology is altered due to F-actin cytoskeleton polarization and the establishment of dynamic focal adhesion spots, which coupled with ECM remodeling enables cells to migrate through tissues seeking a new developmental niche. In our in-depth investigation over the invasive properties triggered by TNBC-derived hypoxic small EVs (SEVh) in vitro, we analyzed the morphological, phenotypical and proteomic distinctions promoted by hypoxia and/or SEVh signaling in TNBC cells. SEVh was fully characterized and showed a distinct proteome and abundance profile from its normoxic counterparts. SEVh promotes invasive behaviors exclusively in normoxia, including pro-migratory morphology, invadopodia development, ECM degradation and gelatinase secretion, which indicates the importance of SEVh response on hypoxic settings in tumor progression. In hypoxia, SEVh was responsible for proteolytic and catabolic pathway inducement, interfering with integrin availability and gelatinase expression. Protein profiling of SEVh-treated, normoxic cells indicate a baseline favoring of metabolic processes and cell cycle, modulating cell health away from apoptotic pathways that are enriched in hypoxia. Overall, our results demonstrate the importance of hypoxic signaling via SEV in a tumoral setting for the early establishment of metastasis.
2022-11-01 | PXD035244 | Pride
Project description:How cancer cells adapt to hypoxia during tumor development remains an important question. The hypothesis tested in the present study was that tumor cell-derived exosome vesicles (also known as microvesicles or extracellular vesicles) are mediators of hypoxia-dependent intercellular signaling in glioblastoma (GBM), i.e. highly aggressive brain tumors characterized by hypoxia and a vascular density that is among the highest of all human malignancies. In vitro hypoxia experiments and studies with patient materials reveal the enrichment in exosomes of hypoxia-regulated mRNAs and proteins, several of which were associated with poor patient prognosis. We show that cancer cell exosomes mediate hypoxia-dependent, phenotypic modulation of stromal cells in vitro and ex vivo, resulting in accelerated GBM tumor angiogenesis and growth in mice. These data suggest that exosomes constitute potent mediators of hypoxia-driven tumor development, and circulating multiparameter biomarkers of tumor hypoxia. U87 MG glioblastoma cells were grown at normoxic (21% oxygen) or hypoxic (1% oxygen) conditions for 48 hours. Conditioned media from normoxic and hypoxic cells were then used to isolate exosomes by differential centrifugation. Both cells and exosomes were lysed in Trizol reagent, and RNA was isolated.Total RNA from all samples (four types of samples in three biological repilicates) was subjected to genome-wide transcriptional analysis with Illumina HumanHT-12 V3.0 expression beadchip. Gene expression profile obtained from hypoxic U87 MG glioblastoma cells was compared to the profile of normoxic control cells. Analogically, gene expression profile obtained from hypoxic U87 MG cells was compared to the profile of exosomes secreted by normoxic U87 MG cells.
2013-03-20 | E-GEOD-45301 | biostudies-arrayexpress
Project description:Dendritic cells (DCs) are professional antigen-presenting cells whose activity is intrinsically linked to the microenvironment. Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues that creates a special microenvironment conditioning cell physiology. We studied the effects of hypoxia on the differentiation of human monocytes into DCs. Immature DCs were differentiated in vitro from human monocytes under normoxic (iDCs) or hypoxic (Hi-DCs) conditions and the gene expression profile was determined. Hi-DCs expressed novel hypoxia-inducible genes and were characterized by up-regulation of pathways associated with cell movement/migration. Keywords: stress response, cell differentiation
2007-01-27 | GSE6863 | GEO