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 1,189 records · Page 66Linked to original sources

PubMed2005

Expression profile of malignant and nonmalignant lesions of esophagus and stomach: differential activity of functional modules related to inflammation and lipid metabolism.

Adenocarcinomas of stomach and esophagus are frequently associated with preceding inflammatory alterations of the normal mucosa. Whereas intestinal metaplasia of the gastric mucosa is associated with higher risk of malignization, Barrett's disease is a risk factor for adenocarcinoma of the esophagus. Barrett's disease is characterized by the substitution of the squamous mucosa of the esophagus by a columnar tissue classified histopathologically as intestinal metaplasia. Using cDNA microarrays, we determined the expression profile of normal gastric and esophageal mucosa as well as intestinal metaplasia and adenocarcinomas from both organs. Data were explored to define functional alterations related to the transformation from squamous to columnar epithelium and the malignant transformation from intestinal metaplasia to adenocarcinomas. Based on their expression profile, adenocarcinomas of the esophagus showed stronger correlation with intestinal metaplasia of the stomach than with Barrett's mucosa. Second, we identified two functional modules, lipid metabolism and cytokine, as being altered with higher statistical significance. Whereas the lipid metabolism module is active in samples representing intestinal metaplasia and inactive in adenocarcinomas, the cytokine module is inactive in samples representing normal esophagus and esophagitis. Using the concept of relevance networks, we determined the changes in linear correlation of genes pertaining to these two functional modules. Exploitation of the data presented herein will help in the precise molecular characterization of adenocarcinoma from the distal esophagus, avoiding the topographical and descriptive classification that is currently adopted, and help with the proper management of patients with Barrett's disease.

Adenocarcinoma↗

PubMed2004

Gene expression profile of human mesenchymal stem cells during osteogenesis in three-dimensional thermoreversible gelation polymer.

This study attempted to characterize the ability of thermoreversible gelation polymer (TGP) to induce differentiation of human mesenchymal stem cells (hMSC) into osteoblasts. Using a long oligo microarray system consisting of 3760 genes, we compared the expression profiles of the cells in 2-dimensional (2D) culture, 3D culture in collagen gel, and 3D culture in TGP with or without osteogenic induction. Compared to 2D culture, the gene expression profile of hMSC showed almost the same pattern in TGP without osteogenic induction, but 72% of genes (2701/3760) were up-regulated in collagen gel. With osteogenic induction, hMSC showed higher ALP activity and osteocalcin production in TGP as compared to 2D culture. Moreover, up-regulation and down-regulation of osteogenic genes were augmented in 3D culture in TGP as compared to 2D culture. As TGP is chemically synthesized and completely free from pathogen such as prion in bovine spongiform encephalopathy, these results suggest that TGP could be applied clinically to induce osteogenic differentiation of hMSC.

Alkaline Phosphatase↗

PubMed2004

Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray.

Gastric cancer is the fourth leading cause of cancer-related death in the world. Two histologically distinct types of gastric carcinoma, 'intestinal' and 'diffuse', have different epidemiological and pathophysiological features that suggest different mechanisms of carcinogenesis. A number of studies have investigated intestinal-type gastric cancers at the molecular level, but little is known about mechanisms involved in the diffuse type, which has a more invasive phenotype and poorer prognosis. To clarify the mechanisms that underlie its development and/or progression, we compared the expression profiles of 20 laser-microbeam-microdissected diffuse-type gastric-cancer tissues with corresponding noncancerous mucosae by means of a cDNA microarray containing 23,040 genes. We identified 153 genes that were commonly upregulated and more than 1500 that were commonly downregulated in the tumors. We also identified a number of genes related to tumor progression. Furthermore, comparison of the expression profiles of diffuse-type with those of intestinal-type gastric cancers identified 46 genes that may represent distinct molecular signatures of each histological type. The putative signature of diffuse-type cancer exhibited altered expression of genes related to cell-matrix interaction and extracellular-matrix (ECM) components, whereas that of intestinal-type cancer represented enhancement of cell growth. These data provide insight into different mechanisms underlying gastric carcinogenesis and may also serve as a starting point for identifying novel diagnostic markers and/or therapeutic targets for diffuse-type gastric cancers.

Base Sequence↗

PubMed2005

Robust and accurate cancer classification with gene expression profiling.

Robust and accurate cancer classification is critical in cancer treatment. Gene expression profiling is expected to enable us to diagnose tumors precisely and systematically. However, the classification task in this context is very challenging because of the curse of dimensionality and the small sample size problem. In this paper, we propose a novel method to solve these two problems. Our method is able to map gene expression data into a very low dimensional space and thus meets the recommended samples to features per class ratio. As a result, it can be used to classify new samples robustly with low and trustable (estimated) error rates. The method is based on linear discriminant analysis (LDA). However, the conventional LDA requires that the within-class scatter matrix S(w) be nonsingular. Unfortunately, Sw is always singular in the case of cancer classification due to the small sample size problem. To overcome this problem, we develop a generalized linear discriminant analysis (GLDA) that is a general, direct, and complete solution to optimize Fisher's criterion. GLDA is mathematically well-founded and coincides with the conventional LDA when S(w) is nonsingular. Different from the conventional LDA, GLDA does not assume the nonsingularity of S(w), and thus naturally solves the small sample size problem. To accommodate the high dimensionality of scatter matrices, a fast algorithm of GLDA is also developed. Our extensive experiments on seven public cancer datasets show that the method performs well. Especially on some difficult instances that have very small samples to genes per class ratios, our method achieves much higher accuracies than widely used classification methods such as support vector machines, random forests, etc.

Algorithms↗

PubMed2005

In vivo drug-response in patients with leukemic non-Hodgkin's lymphomas is associated with in vitro chemosensitivity and gene expression profiling.

Only a few approaches are available to address the mechanisms of cell death in vivo which are induced by anticancer treatment in patients with malignancies. In this study in vitro chemosensitivity testing of primary peripheral blood leukemic cells of five patients suffering from different leukemic non-Hodgkin's lymphomas was combined with the analysis of the in vivo rate of apoptosis by flow-cytometry (Annexin V and depolarisation of mitochondrial membrane potential (MMP) by JC-1). Furthermore, changes in expression patterns of apoptosis related proteins during chemotherapeutic treatment were detected by Western Blot. Gene expression profiling (HG-U133A, Affymetrix, Santa Clara, CA) was employed to identify common marker genes of in vivo drug response. In vitro chemosensitivity was tested using the cytotoxic agents which the patients were scheduled to receive and was strongly correlated with effective reduction of leukemic lymphoma cells in patients resulting in complete remissions in all five cases. Due to the rapid clearance of apoptotic tumor cells in vivo neither the analysis of the in vivo rate of apoptosis and depolarisation of MMP nor the assessment of expression of regulators of apoptosis showed concordant results concerning the drug response. However, assessment of gene expression during therapy could identify a set of 30 genes to significantly discriminate between samples from patients before treatment compared to samples from the same patients after receiving cytotoxic therapy. Among these 30 genes we found a high proportion of genes associated with apoptotic cell death, cell proliferation and cell cycle signalling including complement lysis inhibitor (clusterin/CLU), beta-catenin interacting protein (ICAT), peroxisome proliferator activated receptor alpha (PPARalpha), TNF alpha converting enzyme (ADAM17/TACE), homeo box A3 (HOX1), inositol polyphosphatase 5-phosphatase type IV (PPI5PIV) and inhibitor of p53 induced apoptosis alpha (IPIA-Alpha/NM23-H6). These results indicate that in vitro chemosensitivity testing and gene expression profiling can successfully be utilised to analyse in vivo drug response in patients with leukemic NHL's and can be used to explore new pathway models of drug-induced cell death in vivo which are independent of different lymphoma subtypes and different treatment regimens.

Adenosine↗

PubMed2006

Comparison of gene expression profiles in mouse primary T cells under normal and prolonged activation.

In order to investigate the global transcriptional change of mouse primary T cells after prolonged activation, we took advantage of a Mouse Genome 430 2.0 Array to assess and compare the overall gene expression profiles of mouse T cells after activated with anti-CD3/CD28 for 18 or 48 h. The results demonstrated that most activation-related genes were preferentially up-regulated in mouse primary T cells after stimulated for 18 h; some apoptotic genes, however, were also found to be moderately up-regulated simultaneously. After the activation of T cells for 48 h, lots of apoptosis-related genes were dramatically up-regulated, followed by the augmentation of activation-induced cell death. In general, the number of differentially expressed genes in T cells after activation over 48 h declined almost in half as compared to that of 18 h. Both microarray and cytokine content analyses revealed that Th1 cytokines, rather than Th2 cytokines, were specifically up-regulated in activated mouse primary T cells. The present study also identified a number of genes that were dramatically up or down-regulated in T cells activated for 48 h for the first time, although the exact functions of these proteins are not known. Our studies provide detailed information on genes expression profiles of mouse primary T cells after normal (18 h) and prolonged activation (48 h); these data may accelerate the understanding of the T cell activation process and offer clues to the therapy of immune diseases.

Animals↗

PubMed2002

Microarray analysis of gene-expression profiles in diffuse large B-cell lymphoma: identification of genes related to disease progression.

To identify genes that are associated with progression of malignant lymphoma, the expression profiles of 18,432 genes were analyzed in diffuse large B-cell lymphomas at early (stages I and II, 6 cases) and advanced stages (stages III and IV, 9 cases) by means of cDNA microarrays. By comparing expression profiles between localized and advanced lymphomas, a number of genes that were differentially expressed were identified: 48 genes with increased expression and 30 genes with reduced expression in advanced-stage diffuse large B-cell lymphomas. Increased expression of MPHOSPH1, RUVBL1, CHN2, PSA and CDC10 genes, and reduced expression of COL1A2, COL4A1, FBLN5, CLECSF6, MIC2, CAV1 and S100A10 genes in the advanced lymphoma group were confirmed by semi-quantitative reverse transcription-PCR. RUVBL1 and PSA expression was further confirmed by real-time quantitative PCR, whose results paralleled the microarray data. The highly expressed genes encode proteins that promote cell proliferation and the genes with reduced expression encode adhesion proteins and target protein for cytotoxic T-lymphocytes. These findings suggested that analysis with cDNA microarrays is a useful approach for identifying genes related to tumor progression and their products could be potential tumor markers or disease-specific targets for anti-tumor therapy.

Adult↗

PubMed2004

Gene expression profiling of renal medullary carcinoma: potential clinical relevance.

BACKGROUND: Renal medullary carcinoma is a rare kidney tumor with highly aggressive behavior. This tumor occurs exclusively in young patients with sickle cell trait or disease. To the authors' knowledge, very little is known to date regarding the underlying molecular genetics of this tumor, and no effective therapy has been established. METHODS: The authors analyzed the gene expression profiles of 2 renal medullary carcinomas from patients with sickle cell trait using microarrays containing 21,632 cyclic DNA (cDNA) clones and compared them with the gene expression profiles of 64 renal tumors. RESULTS: Based on global gene clustering with 3583 selected cDNAs, the authors found a distinct molecular signature of renal medullary carcinoma, which clustered closely with urothelial (transitional cell) carcinoma of the renal pelvis, rather than renal cell carcinoma (RCC). This finding of a significant difference in the gene expression patterns of renal medullary carcinoma compared with RCC suggests that this tumor should not be treated as a conventional RCC but, rather, as a special malignancy. This study also identified genes/proteins that may serve as biomarkers for renal medullary carcinoma or as potential targets of novel therapies. In addition, comparative genomic microarray analysis allowed the authors to predict the lack of chromosomal imbalances in this tumor. CONCLUSIONS: To the authors' knowledge, the current study is the first molecular profiling of renal medullary carcinoma, a rare but highly aggressive kidney carcinoma. The genes that are expressed specifically in this tumor may lead to not only a better understanding of its molecular pathways and discoveries of novel diagnostic markers but also, more important, to effective therapeutic interventions.

Adult↗

PubMed2006

DNA microarray study on gene expression profiles in co-cultured endothelial and smooth muscle cells in response to 4- and 24-h shear stress.

Shear stress, a major hemodynamic force acting on the vessel wall, plays an important role in physiological processes such as cell growth, differentiation, remodelling, metabolism, morphology, and gene expression. We investigated the effect of shear stress on gene expression profiles in co-cultured vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Human aortic ECs were cultured as a confluent monolayer on top of confluent human aortic SMCs, and the EC side of the co-culture was exposed to a laminar shear stress of 12 dyn/cm(2) for 4 or 24 h. After shearing, the ECs and SMCs were separated and RNA was extracted from the cells. The RNA samples were labelled and hybridized with cDNA array slides that contained 8694 genes. Statistical analysis showed that shear stress caused the differential expression (p < or = 0.05) of a total of 1151 genes in ECs and SMCs. In the co-cultured ECs, shear stress caused the up-regulation of 403 genes and down-regulation of 470. In the co-cultured SMCs, shear stress caused the up-regulation of 152 genes and down-regulation of 126 genes. These results provide new information on the gene expression profile and its potential functional consequences in co-cultured ECs and SMCs exposed to a physiological level of laminar shear stress. Although the effects of shear stress on gene expression in monocultured and co-cultured EC are generally similar, the response of some genes to shear stress is opposite between these two types of culture (e.g., ICAM-1 is up-regulated in monoculture and down-regulated in co-culture), which strongly indicates that EC-SMC interactions affect EC responses to shear stress.

Cells, Cultured↗

PubMed2005

Gene expression profile and synovial microcirculation at early stages of collagen-induced arthritis.

A better understanding of the initial mechanisms that lead to arthritic disease could facilitate development of improved therapeutic strategies. We characterized the synovial microcirculation of knee joints in susceptible mouse strains undergoing intradermal immunization with bovine collagen II in complete Freund's adjuvant to induce arthritis (i.e. collagen-induced arthritis [CIA]). Susceptible DBA1/J and collagen II T-cell receptor transgenic mice were compared with CIA-resistant FVB/NJ mice. Before onset of clinical symptoms of arthritis, in vivo fluorescence microscopy of knee joints revealed marked leucocyte activation and interaction with the endothelial lining of synovial microvessels. This initial inflammatory cell response correlated with the gene expression profile at this disease stage. The majority of the 655 differentially expressed genes belonged to classes of genes that are involved in cell movement and structure, cell cycle and signal transduction, as well as transcription, protein synthesis and metabolism. However, 24 adhesion molecules and chemokine/cytokine genes were identified, some of which are known to contribute to arthritis (e.g. CD44 and neutrophil cytosolic factor 1) and some of which are novel in this respect (e.g. CC chemokine ligand-27 and IL-13 receptor alpha1). Online in vivo data on synovial tissue microcirculation, together with gene expression profiling, emphasize the potential role played by early inflammatory events in the development of arthritis.

Animals↗

PubMed2006

Functional annotation of IFN-alpha-stimulated gene expression profiles from sensitive and resistant renal cell carcinoma cell lines.

The antiproliferative, antiviral, and immunomodulatory properties of interferons (IFNs) have led to its therapeutic implementation. IFNs effects are mediated by a complex network of signal transducers, culminating in IFN-stimulated gene (ISG) induction. This complexity leads to diverse clinical responses to IFN, from no response to complete regression of disease. Elucidation of ISG induction patterns is, therefore, essential to understand and maximize its therapeutic potential. To correlate ISG expression profiles with IFN responsiveness, two renal cell carcinoma (RCC) cell lines differing in antiviral and apoptotic response to IFN were treated with IFN-alpha for different times, and expression profiles were analyzed using a customized microarray containing 850 unique putative ISGs. Genes with similar kinetics of induction in both cell lines were clustered and analyzed for gene function. Seven sets of coordinately regulated genes were identified by k-means cluster analysis, and significant functional similarities were identified for five of the seven sets. Strikingly, expression of genes associated with transcription temporally preceded expression of those involved in signal transduction. Enhanced antiviral sensitivity to IFN was coincident with sustained expression of ISGs involved in transcriptional regulation. However, no difference in Stat1 activation was observed between the cell lines. Analysis of ISG expression patterns suggests that subtle differences in transcription profiles contribute to differences in IFN responsiveness.

Antineoplastic Agents↗

PubMed2005

Molecular classification of renal tumors by gene expression profiling.

Renal tumor classification is important because histopathological subtypes are associated with distinct clinical behavior. However, diagnosis is difficult because tumor subtypes have overlapping microscopic characteristics. Therefore, ancillary methods are needed to optimize classification. We used oligonucleotide microarrays to analyze 31 adult renal tumors, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, oncocytoma, and angiomyolipoma. Expression profiles correlated with histopathology; unsupervised algorithms clustered 30 of 31 tumors according to appropriate diagnostic subtypes while supervised analyses identified significant, subtype-specific expression markers. Clear cell RCC overexpressed proximal nephron, angiogenic, and immune response genes, chromophobe RCC oncocytoma overexpressed distal nephron and oxidative phosphorylation genes, papillary RCC overexpressed serine protease inhibitors, and extracellular matrix products, and angiomyolipoma overexpressed muscle developmental, lipid biosynthetic, melanocytic, and distinct angiogenic factors. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry of formalin-fixed renal tumors confirmed overexpression of proximal nephron markers (megalin/low-density lipoprotein-related protein 2, alpha-methylacyl CoA racemase) in clear cell and papillary RCC and distal nephron markers (beta-defensin 1, claudin 7) in chromophobe RCC/oncocytoma. In summary, renal tumor subtypes were classified by distinct gene expression profiles, illustrating tumor pathobiology and translating into novel molecular bioassays using fixed tissue.

Gene Expression Profiling↗

PubMed2002

Deciphering the gene expression profile of long-lived snell mice.

In a recent publication, gene expression profiling experiments for the long-lived Snell dwarf mouse were reported. In this Perspective, the author argues that although the authors have developed a solid analytical approach, further refinements are needed to produce robust conclusions.

Animals↗

PubMed2001

Uncovering BRCA1-regulated signalling pathways by microarray-based expression profiling.

The introduction of microarray technology to the scientific and medical communities has dramatically changed the way in which we now address basic biomedical questions. Expression profiling using microarrays facilitates an experimental approach where alterations in the transcript level of entire transcriptomes can be simultaneously assayed in response to defined stimuli. We have used microarray analysis to identify downstream transcriptional targets of the BRCA1 (Breast Cancer 1) tumour-suppressor gene as a means of defining its function. BRCA1 has been implicated in the predisposition to early onset breast and ovarian cancer and while its exact function remains to be defined, roles in DNA repair, cell-cycle control and transcriptional regulation have been implied. In the current study we have generated cell lines with tetracycline-regulated, inducible expression of BRCA1 as a tool to identify genes, which might represent important effectors of BRCA1 function. Oligonucleotide array-based expression profiling identified a number of genes that were upregulated at various times following inducible expression of BRCA1 including the DNA damage-responsive gene GADD45 (Growth Arrest after DNA Damage). Identified targets were confirmed by Northern blot analysis and their functional significance as BRCA1 targets examined.

BRCA1 Protein↗

PubMed2005

MicroRNA expression profiles classify human cancers.

Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.

Animals↗

PubMed2006

Integrated gene expression profiling and linkage analysis in the rat.

The combined application of genome-wide expression profiling from microarray experiments with genetic linkage analysis enables the mapping of expression quantitative trait loci (eQTLs) which are primary control points for gene expression across the genome. This approach allows for the dissection of primary and secondary genetic determinants of gene expression. The cis-acting eQTLs in practice are easier to investigate than the trans-regulated eQTLs because they are under simpler genetic control and are likely to be due to sequence variants within the gene itself or its neighboring regulatory elements. These genes are therefore candidates both for variation in gene expression and for contributions to whole-body phenotypes, particularly when these are located within known and relevant physiologic QTLs. Multiple trans-acting eQTLs tend to cluster to the same genetic location, implying shared regulatory control mechanisms that may be amenable to network analysis to identify gene clusters within the same metabolic pathway. Such clusters may ultimately underlie development of individual complex, whole-body phenotypes. The combined expression and linkage approach has been applied successfully in several mammalian species, including the rat which has specific features that demonstrate its value as a model for studying complex traits.

Animals↗

PubMed2005

Characterization and expression profile analysis of a new cDNA encoding taxadiene synthase from Taxus media.

A full-length cDNA encoding taxadiene synthase (designated as TmTXS), which catalyzes the first committed step in the Taxol biosynthetic pathway, was isolated from young leaves of Taxus media by rapid amplification of cDNA ends (RACE). The full-length cDNA of TmTXS had a 2586 bp open reading frame (ORF) encoding a protein of 862 amino acid residues. The deduced protein had isoelectric point (pI) of 5.32 and a calculated molecular weight of about 98 kDa, similar to previously cloned diterpene cyclases from other Taxus species such as T. brevifolia and T. chinenisis. Sequence comparison analysis showed that TmTXS had high similarity with other members of terpene synthase family of plant origin. Tissue expression pattern analysis revealed that TmTXS expressed strongly in leaves, weak in stems and no expression could be detected in fruits. This is the first report on the mRNA expression profile of genes encoding key enzymes involved in Taxol biosynthetic pathway in different tissues of Taxus plants. Phylogenetic tree analysis showed that TmTXS had closest relationship with taxadiene synthase from T. baccata followed by those from T. chinenisis and T. brevifolia. Expression profiles revealed by RT-PCR under different chemical elicitor treatments such as methyl jasmonate (MJ), silver nitrate (SN) and ammonium ceric sulphate (ACS) were also compared for the first time, and the results revealed that expression of TmTXS was all induced by the tested three treatments and the induction effect by MJ was the strongest, implying that TmTXS was high elicitor responsive.

Amino Acid Sequence↗

PubMed2003

Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse.

Current models of prostate cancer classification are poor at distinguishing between tumors that have similar histopathological features but vary in clinical course and outcome. Here, we applied classical survival analysis to genome-wide gene expression profiles of prostate cancers and preoperative prostate-specific antigen (PSA) levels from each patient, to identify prognostic markers of disease relapse that provide additional predictive value relative to PSA concentration. Three of approximately 200 probesets showing strongest correlation with relapse were identified as the gene for the putative calcium channel protein, trp-p8, with loss of trp-p8 mRNA expression associated with a significantly shorter time to PSA relapse-free survival. We observed subsequently that trp-p8 is lost in the transition to androgen independence in a prostate cancer xenograft model and in prostate cancer tissue from patients treated preoperatively with antiandrogen therapy, suggesting that trp-p8 is androgen regulated, and its loss may be associated with more advanced disease. The identification of trp-p8 and other proteins implicated in the phosphatidylinositol signal transduction pathway that are associated with prostate cancer outcome, both here and in other published work, suggests an integral role for this pathway in prostate carcinogenesis. Thus, our findings demonstrate that multivariable survival analysis can be applied to gene expression profiles of prostate cancers with censored follow-up data and used to identify molecular markers of prostate cancer relapse with strong predictive power and relevance to the etiology of this disease.

Animals↗