SEARCH · PubMed Health

Results for “expression profiling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources

PubMed2004

Two prognostically significant subtypes of high-grade lung neuroendocrine tumours independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles.

BACKGROUND: Classification of high-grade neuroendocrine tumours (HGNT) of the lung currently recognises large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC) as distinct groups. However, a similarity in histology for these two carcinomas and uncertain clinical course have led to suggestions that a single HGNT classification would be more appropriate. Gene expression profiling, which can reproduce histopathological classification, and often defines new subclasses with prognostic significance, can be used to resolve HGNT classification. METHODS: We used cDNA microarrays with 40?386 elements to analyse the gene expression profiles of 38 surgically resected samples of lung neuroendocrine tumours and 11 SCLC cell lines. Samples of large-cell carcinoma, adenocarcinoma, and normal lung were also included to give a total of 105 samples analysed. The data were subjected to filtering to yield informative genes before unsupervised hierarchical clustering that identified relatedness of tumour samples. FINDINGS: Distinct groups for carcinoids, large-cell carcinoma, adenocarcinoma, and normal lung were readily identified. However, we were unable to distinguish LCNEC from SCLC by gene expression profiling. Three independent rounds of unsupervised hierarchical clustering consistently divided SCLC samples into two main groups with LCNEC samples largely integrated with these groups. Furthermore, patients in one of the groups identified by clustering had a significantly better clinical outcome than the other (83% vs 12% survived for 5 years; p=0.0094. None of the highly proliferative SCLC cell lines subsequently analysed clustered with this good-prognosis group. INTERPRETATION: Our findings show that HGNT of the lung can be classified into two groups independent of SCLC and LCNEC. To this end, we have identified many genes, some of which encode well-characterised markers of cancer that distinguish the HGNT groups. These results have implications for the diagnosis, classification, and treatment of lung neuroendocrine tumours, and provide important insights into their underlying biology.

Biomarkers, Tumor↗

PubMed2003

Gene expression profiling in childhood acute leukemia: progress and perspectives.

Recent advances in treatment have transformed childhood acute leukemias into curable diseases. However, 20% to 40% of acute leukemia patients still experience a relapse. Microarrays typically contain thousands of oligonucleotides or complementary DNAs and are rapidly becoming important research tools for the identification of novel classifications of leukemias and lymphomas. Microarray-based identification of several translocations has been performed in acute lymphoblastic leukemia (ALL), leading to the discovery of t(1;19), t(12;21), and 11q23 translocations, and in acute myeloid leukemia (AML), finding t(8;21), inv(16), and t(15;17). Correlations between gene expression profiles and clinical features have been reported in ALL and AML. Recently, it was reported that gene expression profiling can be used to predict the prognosis of childhood acute leukemia. In this report, the recent progress in microarray analysis of childhood acute leukemia is reviewed. Gene expression profiling provides new insights into the biological mechanisms of leukemogenesis and the prognosis of childhood acute leukemia.

Animals↗

PubMed2005

[Study of the expression profile of immunogenesis associated genes in tuberculosis by microarray].

OBJECTIVE: To explore the difference of gene expression profile in tuberculosis patients. METHODS: mRNA levels of pleural fluid and peripheral blood mononuclear cells (PBMC) in tuberculous pleurisy and lung cancer patients were compared by cDNA microarray. Paired mRNAs from fluid specimens of tuberculosis and lung cancer cases were labeled with different fluorochromes during cDNA probe synthesis in a reverse-transcription reaction. The signal intensity of each spot was measured by laser scanner and gene expression was quantified as the tubercle-to-normal fluorescence ratio (T:N ratio). The gene was defined as over expression when the T:N ratio was greater than 2.0 and under expression when the ratio was less than 0.5. RESULTS: Among 626 immunogenesis associated genes there were 53 differences, of which 31 (tnf-alpha, ig-lambda, il-17, il-17r, hla-dp, lcp1, tcralpha, tcrbeta, hsp75, cxcr4, fyb, hla-g, hla-a, il18bp, il-2r, lt-beta, il-8, ip-10, mcp-1, il-12, il-12r, il-10, canx, irf2, ifn-gamma, tlr, il-1, il-7, tlr, lsp-1, il-14)were higher and 22 (il-4, il-18, il-15, ifg-1, scya14, ablim, peci, ppid, hsf 2, actg2, maoa, ttid, gatm, tgfb3, insr, thbd, trap1, tcrgamma, tcrdelta, il-13r, il-11, igf1, a2m)were lower in tuberculous pleurisy than those in the control. CONCLUSIONS: The immunogenesis of tuberculosis involves multi-genetic expression changes, such as tnf-alpha, il-17, il-12, tcralpha, tcrbeta, hsp75, cxcr4, il-4, il-18, il-15 etc., the expression profile of which changed dramatically. The results provide new insight for understanding of the pathogenic mechanisms of tuberculosis and exploring new therapeutic strategies.

Adult↗

PubMed2002

DNA microarray analysis reveals novel gene expression profiles in collagen-induced arthritis.

Global gene expression was analyzed in early and late collagen-induced arthritis (CIA). Of 8734 cDNAs analyzed, 330 were induced and 55 downregulated greater than twofold in early or late disease. Hierarchical clustering of these 385 cDNAs demonstrated five distinct expression patterns differentiating early from late disease and correlating with histopathologic changes in the paw. Of the 385 cDNAs, 185 are known, characterized genes, the majority of which are not described as playing a role in arthritis. However, several of these genes are involved in pathological processes relating to arthritis, including apoptosis, inflammation, and cellular proliferation. One interesting gene, follistatin-like gene, is highly expressed along the margin of contact between inflammatory synovial pannus and eroding bone, suggesting a role in joint destruction. These results demonstrate that global gene expression profiles distinguish early and late CIA and reveal several genes novel to arthritis the further characterization of which will advance our understanding of arthritis.

Animals↗

PubMed2002

Gene and protein expression profiles of Shewanella oneidensis during anaerobic growth with different electron acceptors.

Changes in mRNA and protein expression profiles of Shewanella oneidenesis MR-1 during switch from aerobic to fumarate-, Fe(III)-, or nitrate-reducing conditions were examined using DNA microarrays and two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). In response to changes in growth conditions, 121 of the 691 arrayed genes displayed at least a two-fold difference in transcript abundance as determined by microarray analysis. Genes involved in aerobic respiration encoding cytochrome c and d oxidases and TCA cycle enzymes were repressed under anaerobic conditions. Genes induced during anaerobic respiration included those involved in cofactor biosynthesis and assembly (moaACE, ccmHF, nosD, cysG), substrate transport (cysUP, cysTWA, dcuB), and anaerobic energy metabolism (dmsAB, psrC, pshA, hyaABC, hydA). Transcription of genes encoding a periplasmic nitrate reductase (napBHGA), cytochrome c552, and prismane was elevated 8- to 56-fold in response to the presence of nitrate, while cymA, ifcA, and frdA were specifically induced three- to eightfold under fumarate-reducing conditions. The mRNA levels for two oxidoreductase-like genes of unknown function and several cell envelope genes involved in multidrug resistance increased two- to fivefold specifically under Fe(III)-reducing conditions. Analysis of protein expression profiles under aerobic and anaerobic conditions revealed 14 protein spots that showed significant differences in abundance on 2-D gels. Protein identification by mass spectrometry indicated that the expression of prismane, dihydrolipoamide succinyltransferase, and alcaligin siderophore biosynthesis protein correlated with the microarray data.

Bacterial Proteins↗

PubMed2005

Gene expression profiling in acute myeloid leukemia.

PURPOSE OF REVIEW: This review deals with the emerging promises of gene expression profiling (GEP) and the currently accumulating knowledge about the classification and the discovery of novel disease entities in clinical acute myeloid leukemia (AML). RECENT FINDINGS: Gene expression profiling studies in AML have shown that known and novel classes of disease can be recognized by unsupervised analyses. Prognostically informative molecular signatures can be deduced. Supervised analyses show that particular clinically relevant subsets of AML can be predicted with high accuracy with minimal sets of genes. SUMMARY: The AML GEP studies published to date show a remarkable level of concordance in findings, especially for similar GEP platforms. This confirms the robustness of the methodology and the promise for future applicability of GEP in clinical diagnostics. For the time being, certain technical hurdles remain to be overcome. These relate, for instance, to the conversion of data between different GEP platforms, the effect of differences between various statistical clustering methods, and the still incomplete understanding of the effect of biologic (eg, morphology) and genetic factors on the expression signature. GEP analyses, perhaps in combination with high-throughput mutation analysis and proteomic approaches, may ultimately result in the establishment of a comprehensive diagnostic approach that will yield a key to the precise pathobiologic nature of AML.

Gene Expression Profiling↗

PubMed2001

Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles.

Microarray technology, which allows one to quantitate the expression of thousands of genes simultaneously, has begun to have a major impact on many different areas of drug discovery and development. The question remains of whether microarray analysis and gene expression signature profiles can be applied to the field of toxicology. To date, there are very few published studies showing the use of microarrays in toxicology and important questions remain regarding the predictability and accuracy of applying gene expression profiles to toxicology. To begin to address these questions, we have treated rats with 15 different known hepatotoxins, including allyl alcohol, amiodarone, Aroclor 1254, arsenic, carbamazepine, carbon tetrachloride, diethylnitrosamine, dimethylformamide, diquat, etoposide, indomethacin, methapyrilene, methotrexate, monocrotaline, and 3-methylcholanthrene. These agents cause a variety of hepatocellular injuries including necrosis, DNA damage, cirrhosis, hypertrophy, and hepatic carcinoma. Gene expression analysis was done on RNA from the livers of treated rats and was compared against vehicle-treated controls. The gene expression results were clustered and compared to the histopathology findings and clinical chemistry values. Our results show strong correlation between the histopathology, clinical chemistry, and gene expression profiles induced by the agents. In addition, genes were identified whose regulation correlated strongly with effects on clinical chemistry parameters. Overall, the results suggest that microarray assays may prove to be a highly sensitive technique for safety screening of drug candidates and for the classification of environmental toxins.

Amiodarone↗

PubMed2003

Gene expression profiling of resting and activated vascular smooth muscle cells by serial analysis of gene expression and clustering analysis.

Migration and proliferation of vascular smooth muscle cells (SMCs) are key events in atherosclerosis. However, little is known about alterations in gene expression upon transition of the quiescent, contractile SMC to the proliferative SMC. We performed serial analysis of gene expression (SAGE) of cultured, human SMCs, either grown under resting circumstances or activated with an atherogenic stimulus. Analysis of tags, representing 47,209 and 47,259 mRNAs from a library of resting and activated SMCs, respectively, identified 105 tags induced and 52 tags repressed greater than fivefold. To evaluate the relevance in SMC biology of unmatched, regulated tags, we performed hierarchical clustering analysis, based on their expression profiles in public SAGE databases, and clustered these novel genes in distinct groups. The regulation in SMCs was confirmed by Northern blotting for representative genes of these groups. Plasminogen activator inhibitor-2 has not been associated with atherosclerosis before and was localized to atherosclerotic lesions.

Gene Expression↗

PubMed2005

Methods for gene expression profiling in dermatology research using DermArray nylon filter DNA microarrays.

Here we present methods of gene expression profiling using nylon filter deoxyribonucleic acid (DNA) microarrays and radiolabeled and nonradiolabeled hybridization probes. DermArray(R) nylon filter DNA microarrays were designed specifically for use in dermatology research. A patent-pending method was used to select approx 4400 highly informative, sequence-verified human cDNA clones for this DNA micro array. Using DermArray(R) filters, biomarkers have been discovered for normal and pathologic cells from skin, and for responses to dermatologic drugs. As an example, gene expression profiling was performed with hydroquinone-treated SKMel-28 cells, a melanoma cell line. Also included are the methods for bioinformatic analysis using Pathwaystrade mark software.

Computational Biology↗

PubMed2003

Expression profiles of acute lymphoblastic and myeloblastic leukemias with ALL-1 rearrangements.

The ALL-1 gene is directly involved in 5-10% of acute lymphoblastic leukemias (ALLs) and acute myeloid leukemias (AMLs) by fusion to other genes or through internal rearrangements. DNA microarrays were used to determine expression profiles of ALLs and AMLs with ALL-1 rearrangements. These profiles distinguish those tumors from other ALLs and AMLs. The expression patterns of ALL-1-associated tumors, in particular ALLs, involve oncogenes, tumor suppressors, antiapoptotic genes, drug-resistance genes, etc., and correlate with the aggressive nature of the tumors. The genes whose expression differentiates between ALLs with and without ALL-1 rearrangement were further divided into several groups, enabling separation of ALL-1-associated ALLs into two subclasses. One of the groups included 43 genes that exhibited expression profiles closely linked to ALLs with ALL-1 rearrangements. Further, there were evident differences between the expression profiles of AMLs in which ALL-1 had undergone fusion to other genes and AMLs with partial duplication of ALL-1. The extensive analysis described here pinpointed genes that might have a direct role in pathogenesis.

Chromosome Aberrations↗

PubMed2003

Expression profiling of up-regulated plant and fungal genes in early and late stages of Medicago truncatula-Glomus mosseae interactions.

Suppression subtractive hybridization (SSH), expression profiling and EST sequencing identified 12 plant genes and six fungal genes that are expressed in the arbuscular mycorrhizal symbiosis between Medicago truncatula and Glomus mosseae. All the plant genes and three of the fungal genes were up-regulated in symbiotic tissues. Expression of 15 of the genes is described for the first time in mycorrhizal roots and two are novel sequences. Six M. truncatula genes were also activated during appressorium formation at the root surface, suggesting a role in this early stage of mycorrhiza establishment, whilst the other six plant genes were only induced in the late stages of mycorrhization and could be involved in the development or functioning of the symbiosis. Phosphate fertilization had no significant influence on expression of any of the plant genes. Expression profiling of G. mosseae genes indicated that two of them may be associated with appressorium development on roots and one with arbuscule formation or function. The other three fungal genes were expressed throughout the life-cycle of G. mosseae.

DNA, Complementary↗

PubMedDate not supplied

Toxicological effects of acrylamide on rat testicular gene expression profile.

Toxicological effects of acrylamide on differential gene expression profile of rat testis were evaluated. Acrylamide induced morphological sperm defects, and decreased sperm concentration in cauda epididymis. Serum testosterone level and Leydig cell viability were also decreased dose-dependently, which resulted in decreased spermatogenesis. Acrylamide-induced histopathological lesions, such as formation of multinucleated giant cells and vacuolation, and numerous apoptotic cells were observed in seminiferous tubules. cDNA microarray analysis revealed that genes related to testicular-functions, apoptosis, cellular redox, cell growth, cell cycle, and nucleic acid-binding were up/down-regulated in testes isolated from acrylamide-treated group (60 mg/kg/day). Acrylamide toxicity appears to increase Leydig cell death and perturb gene expression levels, contributing to sperm defects and various abnormal histopathological lesions including apoptosis in rat testis.

Acrylamide↗

PubMed1998

Towards Arabidopsis genome analysis: monitoring expression profiles of 1400 genes using cDNA microarrays.

cDNA microarrays containing 1443 Arabidopsis thaliana genes were analyzed for expression profiles in major organs of Arabidopsis plants. Novel expression profiles were identified for many coding sequences with putative gene identifications. Expression patterns of novel sequences provided clues to their possible functions. The results demonstrate how microarrays containing a large number of Arabidopsis genes can provide a powerful tool for plant gene discovery, functional analysis and elucidation of genetic regulatory networks.

Arabidopsis↗

PubMed2002

Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity.

Large-scale gene expression profiling was performed on embryo-derived stem cell lines to identify molecular signatures of pluripotency and lineage specificity. Analysis of pluripotent embryonic stem (ES) cells, extraembryonic-restricted trophoblast stem (TS) cells, and terminally-differentiated mouse embryo fibroblast (MEF) cells identified expression profiles unique to each cell type, as well as genes common only to ES and TS cells. Whereas most of the MEF-specific genes had been characterized previously, the majority (67%) of the ES-specific genes were novel and did not include known differentiated cell markers. Comparison with microarray data from embryonic material demonstrated that ES-specific genes were underrepresented in all stages sampled, whereas TS-specific genes included known placental markers. Investigation of four novel TS-specific genes showed trophoblast-restricted expression in cell lines and in vivo, whereas one uncharacterized ES-specific gene, Esg-1, was found to be exclusively associated with pluripotency. We suggest that pluripotency requires a set of genes not expressed in other cell types, whereas lineage-restricted stem cells, like TS cells, express genes predictive of their differentiated lineage.

Animals↗

PubMed2001

Expression profile of active genes in human periodontal ligament and isolation of PLAP-1, a novel SLRP family gene.

Periodontal ligament (PDL) is one of the most important tissues in maintaining the homeostasis of tooth and tooth-supporting tissue, periodontium. In this study, we investigated the expression profile of active genes in the human PDL obtained by collecting sequences with a 3'-directed cDNA library, which faithfully represents the composition of the mRNA population. We succeeded in obtaining a total of 1752 cDNA sequences by sequencing randomly selected clones and identified a total of 1318 different species as gene signatures (GS) by their sequence identity, 344 of which were known genes in the GenBank, and 974 of which were new genes. The resulting expression profile showed that collagen type I and type III were the most abundant genes and that osteogenesis-related proteins, such as SPARC/osteonectin and osteoblast specific factor 2, were highly expressed. By comparing the expression profile of PDL with 44 profiles similarly obtained with unrelated human cell/tissue, nine novel genes, which are probably expressed specifically in PDL, were discovered. Among them, we cloned a full-length cDNA of GS5096, which is frequently expressed in freshly-isolated periodontal tissue. We found that it encodes a novel protein, which is a new member of the class I small leucine-rich repeat proteoglycan family, and designated it PLAP-1 (periodontal ligament associated protein-1). PLAP-1 mRNA expression was confirmed in in vitro-maintained PDL cells and was enhanced during the course of the cytodifferentiation of the PDL cells into mineralized tissue-forming cells such as osteoblasts and cementoblasts. These findings suggest the involvement of PLAP-1 in the mineralized matrix formation in PDL tissues.

Amino Acid Sequence↗

PubMed2006

Comparison of gene expression profiles among papilla, medulla and cortex in rat kidney.

The aim of this study was to compare gene expression profiles in the different kidney regions as the basis for toxicogenomics. Rat kidney was separated into papilla, medulla and cortex, and total RNA was isolated from these and from the whole slice. Gene expression profiling was performed using Affymetrix Rat Genome 230 2.0 Array. When global normalization was applied, the expression of beta-actin or GAPDH varied among the regions. It was considered that such a comparison could not be made, especially between papilla and other portions, since the production of total mRNA in the former was relatively low. In fact, ANOVA was performed on the gene expression values with global normalization in papilla, medulla, cortex, and whole slice, and the numbers of genes appeared to be the highest in papilla. It was also observed that many genes showed their maximum or minimum in the whole slice, which was theoretically impossible. To overcome the problems associated with global normalization, the "percellome" normalization (a way to obtain the values directly related to the copies of mRNA per cell) was employed to compare the regions. In applying this procedure, probe sets with regional difference in expression were efficiently extracted by ANOVA. When they were sorted by the fold difference to other regions, the higher rank was occupied by genes characteristic of the functions of kidney, i.e., channels, transporters and metabolic enzymes. Some of them were consistent with the literature and were related to pathophysiological phenomena. Comprehensive comparison of data of gene expression in the renal anatomical area will greatly enhance studies of the physiological function and mechanism of toxicity in kidney.

Animals↗

PubMed2003

Gene expression profiling in adipose tissue indicates different transcriptional mechanisms of liver X receptors alpha and beta, respectively.

The nuclear receptors liver X receptors (LXR) alpha and beta are important regulators of genes involved in lipid, cholesterol, and carbohydrate metabolism and are highly expressed in mature adipocyte tissue. In this study we show that LXRalpha and LXRbeta are more expressed in brown adipose tissue and subcutaneous white adipose tissue than visceral (gonadal) adipose tissue. Furthermore, we report differences between LXRalpha and LXRbeta in their ability to alter expression of target genes. Gene expression profiling analysis of gonadal white adipose tissue from LXRalpha(-/-) mice and LXRbeta(-/-) mice shows different gene expression patterns in the two LXR-deficient mouse strains. Genes regulated similarly in both KO mouse strains as well as genes regulated in one, but not the other LXR-deficient mouse strain were seen. A number of genes were regulated in opposite directions by the respective LXR isoform. Taken together this suggests that the LXR isoforms might operate through different transcriptional mechanisms as well as common mechanisms. These results are in consonance with the growing body of evidence reporting differences in regulation of gene expression between the two isoforms. Furthermore, gene expression profiling shows altered gene expression patterns in primary mouse embryonic fibroblasts (MEFs) from wild type versus LXRbeta(-/-) mice; MEFs are pluripotent cells with the potential to differentiate into mature adipocytes. These results indicate a role of LXR in early developmental stages of adipose tissue.

Adipose Tissue↗

PubMed2002

[Gene expression profiling using improved SAGE].

Serial analysis of gene expression(SAGE) is an experimental technique designed to gain a direct and quantitative measure of gene expression. The SAGE method is based on the isolation of unique sequence tags(9-10 bp in length) from individual mRNAs and serial concatenation of tags into long DNA molecules for lump-sum sequencing. The SAGE-method can be applied to the studies exploring virtually any kinds of biological phenomena in which changes in cellular transcription are responsible. SAGE is a highly competent technology that can not only give a global gene expression profile of a particular type of cell or tissue, but also facilitate identification a set of specific genes related to the cellular conditions by comparing the profiles constructed for a pair of cells maintained under different conditions. However, the original SAGE method contains several serious intrinsic problems, such as procedural difficulty in library construction, extremely short cDNA tags, and so forth. We therefore modified the procedure to overcome these drawbacks, and applied the improved method to analyze various biological phenomena. In this review, we present an outline of the method, and describe several studies performed using the method as a major strategic tool.

Gene Expression Profiling↗