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Results for “expression profiling”

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PubMed2005

Multi-species microarrays reveal the effect of sequence divergence on gene expression profiles.

Interspecies comparisons of gene expression levels will increase our understanding of the evolution of transcriptional mechanisms and help to identify targets of natural selection. This approach holds particular promise for apes, as many human-specific adaptations are thought to result from differences in gene expression rather than in coding sequence. To date, however, all studies directly comparing interspecies gene expression have been performed on single-species arrays, so that it has been impossible to distinguish differential hybridization due to sequence mismatches from underlying expression differences. To evaluate the severity of this potential problem, we constructed a new multiprimate cDNA array using probes from human, chimpanzee, orangutan, and rhesus. We find a large effect of sequence divergence on hybridization signal, even in the closest pair of species, human and chimpanzee. By comparing single-species array analyses with results from multispecies arrays, we examine how estimates of differential gene expression are affected by sequence divergence. Our results indicate that naive use of single-species arrays in direct interspecies comparisons can yield spurious results.

Animals↗

PubMed2003

Expression profiles of two types of human knee-joint cartilage.

We have performed a comprehensive analysis of gene-expression profiles in human articular cartilage (hyaline cartilage) and meniscus (fibrocartilage) by means of a cDNA microarray consisting of 23,040 human genes. Comparing the profiles of the two types of cartilage with those of 29 other normal human tissues identified 24 genes that were specifically expressed in both cartilaginous tissues; these genes might be involved in maintaining phenotypes common to cartilage. We also compared the cartilage profiles with gene expression in human mesenchymal stem cells (hMSC), and detected 22 genes that were differentially expressed in cells representing the two cartilaginous lineages, 11 specific to each type, which could serve as markers for predicting the direction of chondrocyte differentiation. Our data should also provide useful information about regeneration of cartilage, especially in support of efforts to identify cartilage-specific molecules as potential agents for therapeutic approaches to joint repair.

Biomarkers↗

PubMed2006

Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer.

To characterize the molecular mechanisms involved in the carcinogenesis and progression of small-cell lung cancer (SCLC) and identify molecules to be applied as novel diagnostic markers and/or for development of molecular-targeted drugs, we applied cDNA microarray profile analysis coupled with purification of cancer cells by laser-microbeam microdissection (LMM). Expression profiles of 32,256 genes in 15 SCLCs identified 252 genes that were commonly up-regulated and 851 transcripts that were down-regulated in SCLC cells compared with non-cancerous lung tissue cells. An unsupervised clustering algorithm applied to the expression data easily distinguished SCLC from the other major histological type of non-small cell lung cancer (NSCLC) and identified 475 genes that may represent distinct molecular features of each of the two histological types. In particular, SCLC was characterized by altered expression of genes related to neuroendocrine cell differentiation and/or growth such as ASCL1, NRCAM, and INSM1. We also identified 68 genes that were abundantly expressed both in advanced SCLCs and advanced adenocarcinomas (ADCs), both of which had been obtained from patients with extensive chemotherapy treatment. Some of them are known to be transcription factors and/or gene expression regulators such as TAF5L, TFCP2L4, PHF20, LMO4, TCF20, RFX2, and DKFZp547I048 as well as those encoding nucleotide-binding proteins such as C9orf76, EHD3, and GIMAP4. Our data provide valuable information for better understanding of lung carcinogenesis and chemoresistance.

Antineoplastic Agents↗

PubMed2002

Identification of radiation-specific responses from gene expression profile.

The responses to ionizing radiation (IR) in tumors are dependent on cellular context. We investigated radiation-related expression patterns in Jurkat T cells with nonsense mutation in p53 using cDNA microarray. Expression of 2400 genes in gamma-irradiated cells was distinct from other stimulations like anti-CD3, phetohemagglutinin (PHA) and concanavalin A (ConA) in unsupervised clustering analysis. Among them, 384 genes were selected for their IR-specific changes to make 'RadChip'. In spite of p53 status, every type of cells showed similar patterns in expression of these genes upon gamma-radiation. Moreover, radiation-induced responses were clearly separated from the responses to other genotoxic stress like UV radiation, cisplatin and doxorubicin. We focused on two IR-related genes, phospholipase Cgamma2 (PLCG2) and cytosolic epoxide hydrolase (EPHX2), which were increased at 12 h after gamma-radiation in RT-PCR. TPCK could suppress the induction of these two genes in either of Jurkat T cells and PBMCs, which might suggest the transcriptional regulation of PLCG2 and EPHX2 by NF-kappaB upon gamma-radiation. From these results, we could identify the IR-specific genes from expression profiling, which can be used as radiation biomarkers to screen radiation exposure as well as probing the mechanism of cellular responses to ionizing radiation.

Apoptosis↗

PubMedDate not supplied

DNA-microarrays as tools for the identification of tumor specific gene expression profiles: applications in tumor biology, diagnosis and therapy.

DNA-microarrays allow the analysis of almost the complete gene expression program of tumor samples and normal control samples in a single experiment. This allows the processing of a large number of samples in a reasonable short time. Tumor specific gene expression profiles can be used for molecular tumor classification and as a new diagnostic tool. In addition, the identification of tumor specific genes can help to understand the biology of tumor cells and identified genes can be used for the development of new therapeutic strategies. However, the huge amount of data generated by DNA-microarrays creates new challenges for data analysis. In addition, accuracy and reproducibility of the available techniques require complementary methods for verification of DNA-microarray data.

Child↗

PubMed2003

Difference in gene expression profiles between human CD4+CD25+ and CD4+CD25- T cells.

We studied the gene expression profiles of human CD4+CD25+ and CD4+CD25- T cells by using cDNA microarrays. Our preliminary results indicate that there are likely significant differences in the regulation of apoptosis, cell cycle, cytokine receptor, cell-cell interaction, and stress pathway genes between these two subtypes of T cells.

CD4 Antigens↗

PubMed2004

Gene expression profiling of breast cancers with emphasis of beta-catenin regulation.

To gain molecular understanding of carcinogenesis of breast cancer, gene expression profiles were analyzed using cDNA microarray representing 4,600 cDNAs in 10 breast cancer samples and the adjacent noncancerous breast tissues from the same patients. The alterations in gene expression levels were confirmed by reversetranscription PCR in four randomly selected genes. Genes that were differently expressed in cancer and noncancerous tissues were identified. 106 (of which 55 were known) and 49 (of which 28 were known) genes were up- or down-regulated, respectively, in greater than 60% of the breast cancer samples. In cancer tissues, genes related to cell cycle, transcription, metabolism, cell structure/motility and signal transduction were mostly up-regulated. Furthermore, three cancer tissues showing immunohistochemically aberrant accumulation of beta-catenin in the nucleus and/or cytoplasm revealed down-regulation of Siah and Axin genes and up-regulation of Wnt and c-myc genes. These findings were highly consistent with Wnt signaling pathway associated with beta-catenin regulation previously suggested by others. Our studies, therefore, provide not only a molecular basis to understand biological processes of breast cancer but also useful resources to define the mechanism of beta-catenin expression in tumorigenesis of breast cancer.

Adult↗

PubMed2003

Transcriptional gene expression profiles of HGF/SF-met signaling pathway in colorectal carcinoma.

AIM: To explore the transcriptional gene expression profiles of HGF/SF-met signaling pathway in colorectal carcinoma to understand mechanisms of the signaling pathway at so gene level. METHODS: Total RNA was isolated from human colorectal carcinoma cell line LoVo treated with HGF/SF (80 ng/L) for 48 h. Fluorescent probes were prepared from RNA labeled with cy3-dUTP for the control groups and with cy5-dUTP for the HGF/SF-treated groups through reverse-transcription. The probes were mixed and hybridized on the microarray at 60 degrees for 15-20 h, then the microarray was scanned by laser scanner (GenePix 4000B). The intensity of each spot and ratios of Cy5/Cy3 were analyzed and finally the differentially expressed genes were selected by GenePix Pro 3.0 software. 6 differential expression genes(3 up-regulated genes and 3 down-regulated genes) were selected randomly and analyzed by beta-actin semi-quantitative RT-PCR. RESULTS: The fluorescent intensities of built-in negative control spots were less than 200, and the fluorescent intensities of positive control spots were more than 5000. Of the 4004 human genes analyzed by microarray, 129 genes (holding 3.22 % of the investigated genes) revealed differential expression in HGF/SF-treated groups compared with the control groups, of which 61 genes were up-regulated (holding 1.52 % of the investigated genes) and 68 genes were down-regulated (holding 1.70 % of the investigated genes), which supplied abundant information about target genes of HGF/SF-met signaling. CONCLUSION: HGF/SF-met signaling may up-regulate oncogenes, signal transduction genes, apoptosis-related genes, metastasis related genes, and down-regulate a number of genes. The complexity of HGF/SF-met signaling to control the gene expression is revealed as a whole by the gene chip technology.

Carcinoma↗

PubMed2006

Gene expression profiling of renal cell carcinoma: a DNA macroarray analysis.

OBJECTIVE: To examine differences in gene expression levels between renal cell carcinoma (RCC) tissue and 'normal' appearing renal tissue using a commercially available DNA macroarray. MATERIALS AND METHODS: Tissue was obtained from 47 consecutive radical nephrectomies, 29 of which were eligible. DNA macroarrays were analysed on the tumour and normal-appearing control tissue to measure the expression of 1185 cancer-related genes. The group of samples was also stratified according to the presence or absence of granular cells and according to tumour grade. Quantitative real-time polymerase-chain reaction (PCR) was also performed on seven key genes present on the macroarray. RESULTS: In all, 444 genes were over-expressed and 33 genes were under-expressed. Using selection criteria reduced the list to nine that were significantly over-expressed and 23 that were under-expressed. These significant genes belonged to the families of oncogenes, growth factors, interleukins, receptors, immune system components, cytoskeleton, matrix proteins and intracellular modulators, or they coded for proteins involved in DNA transcription and RNA translation, DNA repair, protein turnover, and metabolism of carbohydrates and lipids. There were differences in gene expression according to the presence or absence of granular cells and according to tumour grade. Using quantitative real-time PCR there was over-expression of epidermal growth factor receptor, c-myc, transforming growth factor-alpha, vascular endothelial growth factor and vimentin, and under-expression of TYRO3 protein tyrosine kinase. The von Hippel-Lindau gene was under-expressed but not significantly. CONCLUSIONS: A procedure for collecting and storing fresh renal tissue and subsequent gene expression profiling of RCC and normal renal tissue was established. A commercially available DNA macroarray coupled with the significance analysis of macroarrays allowed the identification of sets of differentially expressed cancer-related genes that were characteristic of RCC, compared with apparently normal renal tissue, and which distinguished among subgroups divided according to tumour grade and histological subtype. Quantitative PCR is important to validate the results of macroarray experiments.

Carcinoma, Renal Cell↗

PubMed2002

[cDNA microarray technology as a laboratory examination method: a gene expression profiling test for analysis of drug resistance in tumor cells].

cDNA microarray technology permits the simultaneous measurement of the expressions of thousands of genes. The technology is now an indispensable research tool in molecular biology, and the challenge is its development and usage as clinical diagnostic tools. cDNA microarray can be used to identify gene expression profiles in tumor cells which correlate strongly with the treatment responsiveness such as drug resistance and clinical outcome of the disease despite similar phenotypes. For the introduction of cDNA microarray into laboratory examination, many issues need to be resolved. Design of a diagnostic array must be developed with defined sequences based on interpretation of huge quantities of data from experimental arrays to predict treatment responsiveness. Assay quality must be improved in terms of detection sensitivity, reproducibility, and linear dynamic range for RNA quantitation. Generally available instruments, which are much less expensive and more practical, need to be developed. Along with the improvement of the assay as a laboratory examination method, cDNA microarray will facilitate the integration of diagnosis and therapeutics, and the introduction of individual medicines.

Clinical Laboratory Techniques↗

PubMed2006

Effects of Emx2 inactivation on the gene expression profile of neural precursors.

Emx2 plays a crucial role in the development of the diencephalon and dorsal telencephalon. Thus, Emx2-null mutants have abnormal cortical lamination and a reduction in size of the caudal and medial areas of the prosencephalon. Emx2 is expressed in neural precursors of the subventricular zone in vivo and in cultured neurospheres in vitro where it controls the size of the transit-amplifying population, affecting proliferation and clonal efficiency of neural stem cells. To identify the cellular processes mastered by Emx2, and possibly the molecular mechanisms by which the gene exerts its action, we compared the expression profile of cultured neurospheres derived from wild-type and Emx2-null mouse embryos. The differential expression of several genes was also confirmed by semiquantitative RT-PCR, real-time PCR and cytofluorimetric analysis in different preparations of neurospheres, and by in situ hybridization. The gene expression profile suggested a role for Emx2 in regulating the differentiation and migration properties of neural precursor cells. This involvement was confirmed in vitro, where the altered clonogenicity and impaired migration of Emx2-null cells were partially corrected by transduction of the Emx2 gene. Taken together, our results indicate that Emx2 is indeed involved in the transition between resident early progenitors (perhaps stem cells) and more mature precursors capable of migrating out of the ventricular zone, becoming postmitotic and differentiating into the appropriate cell type, and help explain the alterations observed in the brains of knock-out mice.

Animals↗

PubMed2006

Age-dependent alterations in CRMP2 and CRMP4 protein expression profiles in cat visual cortex.

We monitored the protein expression profiles of collapsin response mediator protein 2 and 4 (CRMP2 and CRMP4) throughout cat primary visual area 17 at different postnatal ages. Single immunocytochemical stainings revealed a clear effect of cortical maturation on the spatial and laminar distribution profile of CRMP2 and CRMP4. In kittens of postnatal day 10 (P10) and 30 (P30), CRMP2 and CRMP4 immunoreactivity was exclusively present in fibers running perpendicular to the cortical surface and crossing all cortical layers, but was never found in neuronal cell bodies. The immunoreactive fibers were embedded in an intensely and homogeneously stained neuropil. In contrast, mature visual cortex immunocytochemistry located CRMP2 and CRMP4 in the somatodendritic compartment of neurons with a clear CRMP-specific lamination pattern. Similar to kitten, neuropil staining was clearly observed but showed a decreasing gradient from layer I to VI in adult area 17. Detailed analysis of cellular morphology and size classified the CRMP2- and CRMP4-immunopositive cells in distinct neuronal populations. Double labeling of CRMP2 or CRMP4 with the typical interneuron marker parvalbumin (PV) showed many double-labeled cells immunoreactive for CRMP4 and PV, but not for CRMP2 and PV, corroborating the cell type-specific character of each CRMP. Our present results clearly illustrate that CRMP2 and CRMP4 may play an important role in visual cortex, possibly providing different classes of neurons with the potential to form a functionally meaningful network, not only during development, but also in adulthood, coincident with the belief that CRMPs are involved in neurite growth and guidance.

Animals↗

PubMed2005

Gene-expression profiling predicts recurrence in Dukes' C colorectal cancer.

BACKGROUND & AIMS: Although approximately 50% of Dukes' C colorectal cancer patients are surgically cured, it is currently not possible to distinguish these patients from those at high risk of recurrence. The recent advent of routine adjuvant chemotherapy for these patients has greatly complicated the identification of new markers predicting the response to surgery, which is now reliant on archived materials. Microarray analysis allows fine tumor classification but cannot be used with paraffin-embedded archival samples. METHODS: We used microarray analysis of a unique set of fresh-frozen tumor samples from Dukes' C patients who had surgery as the only form of treatment to identify molecular signatures that characterize tumors from patients with good and bad prognosis. RESULTS: Unsupervised hierarchical clustering and a K-nearest neighbors-based classifier identified groups of patients with significantly different survival (P = .019 and P = .0001). Expression profiling outperformed previously reported genetic markers of prognosis such as TP53 and K-RAS mutational status and allelic imbalance in chromosome 18q, which were of limited prognostic power in this study. Functional categories significantly enriched in gene-expression differences included protein transport and folding. The prognostic potential of the RAS homologue RHOA, one of the most differentially expressed genes, was further investigated using immunohistochemistry and a tissue microarray containing 137 independent Dukes' C tumor samples. Reduced RHOA expression was associated with significantly shorter survival (P = .01). CONCLUSIONS: This study shows that gene-expression profiling of surgical tumor samples can predict recurrence in Dukes' C patients. Therefore, this approach could be used to guide decisions concerning the clinical management of these patients.

Aged↗

PubMedDate not supplied

Gene expression profiling--a new approach in the study of myocardial ischemia.

Current technologies make it possible to study thousands of genes simultaneously in the same biological sample - an approach termed gene expression profiling. Several techniques, including (i) differential display, (ii) serial analysis of gene expression (SAGE), (iii) subtractive hybridization and (iv) gene microarrays (Gene Chips), have been developed. Recently, gene profiling was applied in studying the mechanisms of ischemic injury and ischemic preconditioning. In the case of reversible ischemia caused by one or several brief transient episodes of complete coronary occlusion (as with ischemic preconditioning), or with a more prolonged but partial coronary ligation, many up-regulated genes were related to the "cell survival program". Protective genes included mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK 3), heat shock proteins 70, 27, 22, B-crystalline, vascular endothelial growth factor, inducible nitric oxide synthase and plasminogen activator inhibitors 1 and 2. With permanent coronary occlusion lasting from 24 h to several weeks, and resulting in a true myocardial infarction (MI), the list of up-regulated genes included those related to remodeling (e.g., collagens I and III, fibronectin, laminin) and apoptosis (Bax), while many down-regulated genes were related to major energy-generating pathways in the heart, namely, fatty acid metabolism. Gene expression profiling experiments have resulted in the discovery of two different genetic programs in the heart, namely, a protective program activated upon brief episodes of transient ischemia and an injury-related one activated in response to irreversible ischemic injury. Searching for factors turning on protective genes, and turning down injury-related ones, is a justifiable approach in developing new therapeutic strategies aimed to fight ischemic heart disease.

Gene Expression↗

PubMed2004

Molecular mechanisms of breast cancer progression: lessons from mouse mammary cancer models and gene expression profiling.

The development of breast cancer is thought to occur through a multi-step process. The majority of breast cancers likely develop over extended periods of time arising from early, pre-invasive lesions such as atypical ductal hyperplasia (ADH) and carcinoma in situ (DCIS), progressing to invasive carcinoma and culminating in metastatic disease. However, the molecular mechanisms underlying this process are still poorly understood. The molecular analysis of this multi-step process in human patients is hampered by the difficulty in obtaining tissue samples at all tumor stages, especially from the same patient. In contrast, mouse models of mammary cancer progression are amenable to pathological, genetic and biochemical analyses at all tumor stages. Global gene expression profiling allows for simultaneous interrogation of the expression of thousands of genes and provides important opportunities to identify molecular signatures of tumor progression. This approach provides a means to define networks of cancer-related genes and their potential role in tumor progression. In this review, we discuss mouse models that have contributed substantially to understanding the molecular mechanisms of breast cancer progression and insights gained from gene expression profiling of mouse mammary cancer models and human breast cancer.

Journal Article↗

PubMed2002

Protein expression profiles indicative for drug resistance of non-small cell lung cancer.

Data obtained from multiple sources indicate that no single mechanism can explain the resistance to chemotherapy exhibited by non-small cell lung carcinomas. The multi-factorial nature of drug resistance implies that the analysis of comprising expression profiles may predict drug resistance with higher accuracy than single gene or protein expression studies. Forty cellular parameters (drug resistance proteins, proliferative, apoptotic, and angiogenic factors, products of proto-oncogenes, and suppressor genes) were evaluated mainly by immunohistochemistry in specimens of primary non-small cell lung carcinoma of 94 patients and compared with the response of the tumours to doxorubicin in vitro. The protein expression profile of non-small cell lung carcinoma was determined by hierarchical cluster analysis and clustered image mapping. The cluster analysis revealed three different resistance profiles. The frequency of each profile was different (77, 14 and 9%, respectively). In the most frequent drug resistance profile, the resistance proteins P-glycoprotein/MDR1 (MDR1, ABCB1), thymidylate-synthetase, glutathione-S-transferase-pi, metallothionein, O6-methylguanine-DNA-methyltransferase and major vault protein/lung resistance-related protein were up-regulated. Microvessel density, the angiogenic factor vascular endothelial growth factor and its receptor FLT1, and ECGF1 as well were down-regulated. In addition, the proliferative factors proliferating cell nuclear antigen and cyclin A were reduced compared to the sensitive non-small cell lung carcinoma. In this resistance profile, FOS was up-regulated and NM23 down-regulated. In the second profile, only three resistance proteins were increased (glutathione-S-transferase-pi, O6-methylguanine-DNA-methyltransferase, major vault protein/lung resistance-related protein). The angiogenic factors were reduced. In the third profile, only five of the resistance factors were increased (MDR1, thymidylate-synthetase, glutathione-S-transferase-pi, O6-methylguanine-DNA-methyltransferase, major vault protein/lung resistance-related protein).

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Modes and clustering for time-warped gene expression profile data.

MOTIVATION: The study of the dynamics of regulatory processes has led to increased interest for the analysis of temporal gene expression level data. To address the dynamics of regulation, expression data are collected repeatedly over time. It is difficult to statistically represent the resulting high-dimensional data. When regulatory processes determine gene expression, time-warping is likely to be present, i.e. the sample of gene expression trajectories reflects variation not only in terms of the expression amplitudes, but also in terms of the temporal structure of gene expression. RESULTS: A non-parametric time-synchronized iterative mean updating technique is proposed to find an overall representation that corresponds to a mode of a sample of expression profiles, viewed as a random sample in function space. The proposed algorithm explores the application of previous work of Hall and Heckman to genome-wide expression data and provides an extension that includes random time-warping with the aim to synchronize timescales across genes. The proposed algorithm is universally applicable for the construction of modes for functional data with time-warping. We demonstrate the construction of mode functions for a sample of Drosophila gene expression data. The algorithm can be applied to define clusters among the observed trajectories of gene expression, without any kind of prior non-time-warped clustering, as illustrated in the numerical example.

Adaptation, Physiological↗

PubMed2005

Gene expression profile differences in gastric cancer, pericancerous epithelium and normal gastric mucosa by gene chip.

AIM: To study the difference of gene expression in gastric cancer (T), pericancerous epithelium (P) and normal tissue of gastric mucosa (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonucleotide microarray. METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results. RESULTS: When gastric cancer was compared with normal gastric mucosa, 766 genes were found, with a difference of more than four times in expression levels. Of the 766 genes, 530 were up-regulated (Signal Log Ratio (SLR) >2), and 236 were down-regulated (SLR<-2). When pericancerous epithelium was compared with normal gastric mucosa, 64 genes were found, with a difference of more than four times in expression levels. Of the 64 genes, 50 were up-regulated (SLR>2), and 14 were down-regulated (SLR<-2). Compared with normal gastric mucosa, a total of 143 genes with a difference in expression levels (more than four times, either in cancer or in pericancerous epithelium) were found in gastric cancer (T) and pericancerous epithelium (P). Of the 143 genes, 108 were up-regulated (SLR>2), and 35 were down-regulated (SLR<-2). CONCLUSION: To apply a gene chip could find 143 genes associated with the genes of gastric cancer in pericancerous epithelium, although there were no pathological changes in the tissue slices. More interesting, six genes of pericancerous epithelium were up-regulated in comparison with genes of gastric cancer and three genes were down-regulated in comparison with genes of gastric cancer. It is suggested that these genes may be related to the carcinogenesis and development of early gastric cancer.

Epithelium↗