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Expression profiling identifies genes involved in emphysema severity.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients.Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples.Class comparison identified 98 differentially expressed genes (p < 0.01). Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05. Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity.Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3.

SUBMITTER: Francis SM

PROVIDER: S-EPMC2746189 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Expression profiling identifies genes involved in emphysema severity.

Francis Santiyagu M Savarimuthu SM Larsen Jill E JE Pavey Sandra J SJ Bowman Rayleen V RV Hayward Nicholas K NK Fong Kwun M KM Yang Ian A IA

Respiratory research 20090902

Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients.Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-P ...[more]

PMID: 19723343

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Project description:BackgroundGene expression technologies have the ability to generate vast amounts of data, yet there often resides only limited resources for subsequent validation studies. This necessitates the ability to perform sorting and prioritization of the output data. Previously described methodologies have used functional pathways or transcriptional regulatory grouping to sort genes for further study. In this paper we demonstrate a comparative genomics based method to leverage data from animal models to prioritize genes for validation. This approach allows one to develop a disease-based focus for the prioritization of gene data, a process that is essential for systems that lack significant functional pathway data yet have defined animal models. This method is made possible through the use of highly controlled spotted cDNA slide production and the use of comparative bioinformatics databases without the use of cross-species slide hybridizations.ResultsUsing gene expression profiling we have demonstrated a similar whole transcriptome gene expression patterns in prostate cancer cells from human and rat prostate cancer cell lines both at baseline expression levels and after treatment with physiologic concentrations of the proposed chemopreventive agent Selenium. Using both the human PC3 and rat PAII prostate cancer cell lines have gone on to identify a subset of one hundred and fifty-four genes that demonstrate a similar level of differential expression to Selenium treatment in both species. Further analysis and data mining for two genes, the Insulin like Growth Factor Binding protein 3, and Retinoic X Receptor alpha, demonstrates an association with prostate cancer, functional pathway links, and protein-protein interactions that make these genes prime candidates for explaining the mechanism of Selenium's chemopreventive effect in prostate cancer. These genes are subsequently validated by western blots showing Selenium based induction and using tissue microarrays to demonstrate a significant association between downregulated protein expression and tumorigenesis, a process that is the reverse of what is seen in the presence of Selenium.ConclusionsThus the outlined process demonstrates similar baseline and selenium induced gene expression profiles between rat and human prostate cancers, and provides a method for identifying testable functional pathways for the action of Selenium's chemopreventive properties in prostate cancer.

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Project description:BackgroundJatropha curcas, a tropical shrub, is a promising biofuel crop, which produces seeds with high content of oil and protein. To better understand the maturation process of J. curcas seeds and to improve its agronomic performance, a two-step approach was performed in six different maturation stages of seeds: 1) generation of the entire transcriptome of J. curcas seeds using 454-Roche sequencing of a cDNA library, 2) comparison of transcriptional expression levels using a custom Agilent 8x60K oligonucleotide microarray.ResultsA total of 793,875 high-quality reads were assembled into 19,382 unique full-length contigs, of which 13,507 could be annotated with Gene Ontology (GO) terms. Microarray data analysis identified 9111 probes (out of 57,842 probes), which were differentially expressed between the six maturation stages. The expression results were validated for 75 selected transcripts based on expression levels, predicted function, pathway, and length. Result from cluster analyses showed that transcripts associated with fatty acid, flavonoid, and phenylpropanoid biosynthesis were over-represented in the early stages, while those of lipid storage were over-represented in the late stages. Expression analyses of different maturation stages of J. curcas seed showed that most changes in transcript abundance occurred between the two last stages, suggesting that the timing of metabolic pathways during seed maturation in J. curcas occurs in late stages. The co-expression results showed that the hubs (CB5-D, CDR1, TT8, DFR, HVA22) with the highest number of edges, associated with fatty acid and flavonoid biosynthesis, are showing a decrease in their expression during seed maturation. Furthermore, seed development and hormone pathways are significantly well connected.ConclusionThe obtained results revealed differentially expressed sequences (DESs) regulating important pathways related to seed maturation, which could contribute to the understanding of the complex regulatory network during seed maturation with the focus on lipid, flavonoid and phenylpropanoid biosynthesis. This study provides detailed information on transcriptional changes during J. curcas seed maturation and provides a starting point for a genomic survey of seed quality traits. The results highlighted specific genes and processes relevant to the molecular mechanisms involved in Jatropha seed maturation. These data can also be utilized regarding other Euphorbiaceae species.

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Expression profiling identifies genes involved in emphysema severity.

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Expression profiling identifies genes involved in emphysema severity.

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