Project description:This 58 arrays are the basis of our hypoxia story published in PLoS Medicine. The cell type, oxygen tension and time points are indicated. Abstract: BACKGROUND: Inadequate oxygen (hypoxia) triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis in breast and ovarian cancer. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set

Project description:This 58 arrays are the basis of our hypoxia story published in PLoS Medicine. The cell type, oxygen tension and time points are indicated. Abstract: BACKGROUND: Inadequate oxygen (hypoxia) triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis in breast and ovarian cancer. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Using regression correlation

Project description:Recently, increasing studies suggested that lncRNA SNHG12 was aberrantly expressed in kinds of cancers. However, definite prognostic value of SNHG12 remains unclear. We conducted this meta-analysis to evaluate the association between SNHG12 expression level and cancer prognosis. A literature retrieval was conducted by searching kinds of databases. The meta-analysis was performed by using Revman 5.2 and Stata 12.0 software. Besides, The Cancer Genome Atlas dataset was analyzed to validate the results in our meta-analysis via using Gene Expression Profiling Interactive Analysis. The pooled results showed that high SNHG12 expression significantly indicated worse overall survival and recurrence-free survival. Tumor type, sample size, survival analysis method, and cutoff value did not alter SNHG12 prognosis value according to stratified analysis results. Additionally, higher expression of SNHG12 suggested unfavorable clinicopathological outcomes including larger tumor size, lymph node metastasis, distant metastasis, and advanced clinical stage. Online cross-validation in TCGA dataset further indicated that cancer patients with upregulated SNHG12 expression had worse overall survival and disease-free survival. Therefore, elevated SNHG12 expression was associated with poor survival and unfavorable clinical outcomes in various cancers, and therefore might be a potential prognostic biomarker in human cancers. Abbreviations Akt: protein kinase B; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; ceRNA: competitive endogenous RNA; CNKI: China National Knowledge Infrastructure; CI: confidence interval; CCNE1: cyclin E1; COAD: colon adenocarcinoma; DM: distant metastasis; DFS: disease-free survival; EMT: epithelial-mesenchymal transition; FISH: fluorescence in situ hybridization; FIGO: the International Federation of Gynecology and Obstetrics; GEPIA: Gene Expression Profiling Interactive Analysis; HR: hazard ratio; HIFα: hypoxia-inducible factor 1 α; KIRC: kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; LIHC: hepatocellular carcinoma; LNM: lymph node metastasis; mTOR: mechanistic target of rapamycin kinase; MMP-9: matrix metalloproteinase 9; MCL1: myeloid cell leukemia 1; MLK3: mixed-lineage protein kinase 3; N/A: not available; NOS: Newcastle-Ottawa Scale; OR: odd ratio; OS: overall survival; PSA: prostate-specific antigen; PI3K: phosphoinositide 3-kinase; qRT-PCR: quantitative real-time polymerase chain reaction; READ: rectum adenocarcinoma; RFS: recurrence-free survival; SARC: sarcoma; SNHG12: small nucleolar RNA host gene 12; STAT3: signal transducer and activator of transcription 3; SOX4: SRY-box transcription factor 4; SOX5: SRY-box transcription factor 5; STAD: stomach adenocarcinoma; TCGA: The Cancer Genome Atlas; TNM: tumor node metastasis; WWP1: WW domain-containing E3 ubiquitin protein ligase 1; WHO grade: World Health Organization grade; ZEB2: zinc finger E-box-binding homeobox 2.

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Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers.

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