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Results for “Expression profiling”

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At least 1,531 records · Page 85Linked to original sources

PubMed2005

Gene expression profiling of NMU-induced rat mammary tumors: cross species comparison with human breast cancer.

Breast cancer is a complex genetic disease characterized by the accumulation of multiple molecular alterations. The NMU breast cancer model induced in the rat is used for the study of mammary carcinogenesis because it closely mimics human breast disease. To assess the validity of this model from a more global molecular perspective, and also to devise a general technique to compare animal profiles with human microarray studies, we have characterized 25 NMU-induced mammary tumors and 11 normal glands using a combination of immunohistochemical and microarray analyses. The rat mammary carcinomas were classified as non-invasive, ER-positive ductal carcinomas with a composition of differentiated epithelial and myoepithelial cell lineages. Gene expression profiles generated using rat Affymetrix arrays containing 15,866 genes demonstrated that the rat mammary tumors are homogeneous and that H-ras mutations did not confer a unique molecular signature. We compared the resulting rat profiles with those obtained from a human dataset by merging the raw microarray data, using an approach that involves a combination of cross-species and cross-platform analysis. Using this novel strategy, we demonstrate the ability of 2305 rat orthologs to recapitulate the classification of human tumors derived from human Affymetrix arrays. The gene expression profiles of the NMU-induced primary tumors were most similar to ER-positive, low to intermediate grade breast cancer. Our technique provides a means to correlate gene expression data from animal models of cancer to human cancer and disease states.

Animals↗

PubMed2004

Gene expression profiling of scrapie-infected brain tissue.

The underlying pathomechanisms in prion infections of the central nervous system are still insufficiently understood. The identification of genes with altered expression patterns in the diseased brain may provide insight into the disease development on the molecular level, which ultimately leads to neuronal loss. To provide a detailed analysis of changes in the molecular level in prion disease pathology we used a large-scale gene array based approach, which covers more than 11,000 functionally characterised sequences and expressed sequence tags, for the analysis of gene expression profile alterations in the cortex, medulla, and pons of scrapie-infected mice. The study identified in total 114 genes with altered mRNA levels, the majority of which were previously not known to be affected by the disease. Overall the gene array data demonstrate the presence of a strong inflammatory reaction and stress response, and show similarities to gene expression patterns found in brains affected by Alzheimer's disease and aging, respectively.

Animals↗

PubMed2005

Gene expression profiles of intact and regenerating zebrafish retina.

PURPOSE: Investigate the molecular determinants of retinal regeneration in adult vertebrates by analyzing the gene expression of control and post-lesion retina of adult zebrafish, a system that regenerates following injury. METHODS: Gene expression of zebrafish retina and brain were determined with DNA microarray, RT-PCR, and real-time quantitative PCR analyses. Damaged retinas and their corresponding controls were analyzed 2-5 days post-lesion (acute injury condition) or 14 d post-lesion (cell regeneration condition). RESULTS: Expected similarities and differences in the gene expression profile of zebrafish retina and brain were observed, confirming the applicability of the gene expression techniques. Mechanical lesion of retina triggered significant, time-dependent changes in retinal gene expression. The induced transcriptional changes were consistent with cellular phenomena known to occur, in a time-dependent manner, subsequent to retinal lesion, including cell cycle progression, axonal regeneration, and regenerative cytogenesis. CONCLUSIONS: The results indicate that retinal regeneration in adult zebrafish involves a complex set of induced, targeted changes in gene transcription, and suggest that these molecular changes underlie the ability of the adult vertebrate retina to regenerate.

Animals↗

PubMedDate not supplied

Classification of sensitivity or resistance of cervical cancers to ionizing radiation according to expression profiles of 62 genes selected by cDNA microarray analysis.

To identify a set of genes related to radiosensitivity of cervical squamous cell carcinomas and to establish a predictive method, we compared expression profiles of 9 radiosensitive and 10 radioresistant tumors obtained by biopsy before treatment, on a cDNA microarray consisting of 23,040 human genes. We identified 121 genes whose expression was significantly greater in radiosensitive cells than in radioresistant cells, and 50 genes that showed higher levels of expression in radioresistant cells than in radiosensitive cells. Some of these genes had already known to be associated with the radiation response, such as aldehyde dehydrogenase 1 (ALDH1) and X-ray repair cross-complementing 5 (XRCC5) (P<.05, Mann-Whitney test). The validity of the total of 171 genes as radiosensitivity related genes were certified by permutation test (P<.05). Furthermore, we selected 62 genes on the basis of a clustering analysis, and confirmed the validity of these genes with cross-validation test. The cross-validation test also indicates the possibility of making prediction of radiosensitivity for discriminating radiation-sensitive from radiation resistant biopsy samples by predicting score (PS) values calculated from expression values of 62 genes in 19 samples, because the prediction successfully and unequivocally discriminated the radiosensitive phenotype from the radioresistant phenotype in our test panel of 19 cervical carcinomas. The extensive list of genes identified in these experiments provides a large body of potentially valuable information for studying the mechanism(s) of radiosensitivity, and selected 62 genes opens the possibility of providing appropriate and effective radiotherapy to cancer patients.

Aged↗

PubMed2001

Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma, and normal tissue examined by oligonucleotide arrays.

Using an oligonucleotide array containing sequences complementary to approximately 3200 full-length human cDNAs and 3400 expressed sequence tags (GeneChip, Affymetrix), mRNA expression patterns were probed in 18 colon adenocarcinomas and 4 adenomas. Paired normal tissue was available and analyzed for each of the tumors. Relatively few changes in transcript expression are associated with colon cancer. Nineteen transcripts (0.48% of those detected) had at least 4-10.5-fold higher mRNA expression in carcinoma compared with paired normal samples, whereas 47 transcripts (1.3% of those detected) had at least 4-38-fold or lower expression in the tumor tissue compared with the normal samples. Some of these differences were confirmed by reverse transcription-PCR. Many of these transcripts were already known to be abnormally expressed in neoplastic tissue in general, or colon cancer in particular, and several of these differences were also observed in premalignant adenoma samples. A two-way hierarchical clustering algorithm successfully distinguished adenoma from adenocarcinoma and normal tissue, generating a phylogenetic tree that appropriately represented the clinical relationship between the three tissue types included in the analysis. This supports the concept that genome-wide expression profiling may permit a molecular classification of solid tumors.

Adenocarcinoma↗

PubMedDate not supplied

Gene expression profiling of peripheral blood mononuclear leukocytes from psoriasis patients identifies new immune regulatory molecules.

In the present report gene expression profiling of peripheral blood mononuclear cells (PBMC) from psoriasis patients suffering from severe generalized disease was performed comparing diseased stage with cured stage. By this means, 18 genes were identified which showed differential expression. The most significant differences were found for IL-8, annexin A3, cycloxygenase-2 (COX-2), cell cycle regulator G0S2, and pre-B cell enhancing factor (PBEF), all of which showed upregulation in the diseased stage. Microarray data were confirmed by real-time RT-PCR. Further analyses using support vector machines identified three pairs of genes (IL-8 - CDKN1C/p57, cyclooxygenase-2 - NR1D2, and desmocollin-2 - CDKN1C/p57) which allowed an accuracy of disease stage prediction of 86%, based on gene expression patterns. Taken together, this is the first large-scale gene expression study of psoriasis PBMC identifying candidate genes that might contribute to psoriasis immunopathogenesis. The genes identified in the present report and the molecular mechanisms underlying their regulation might serve as future targets for therapeutic intervention in psoriasis.

Gene Expression Profiling↗

PubMed2000

Proteasome inhibitor induced gene expression profiles reveal overexpression of transcriptional regulators ATF3, GADD153 and MAD1.

The ubiquitin/proteasome pathway has been implicated in a wide variety of cellular processes and the number of substrates degraded by the proteasome is impressive. Most prominently, the stability of a large number of transcription factors is regulated by ubiquitination. To elucidate pathways regulated by the proteasome, gene expression profiles were generated, comparing changes of mRNA expression of 7900 genes from the UniGene collection upon exposure of cells to the proteasome inhibitors Lactacystin, Lactacystin-beta-lactone or MG132 by means of microarray based cDNA hybridization. The three profiles were very similar, but differed significantly from a gene expression profile generated with the histone deacetylase inhibitor Trapoxin A, indicating that the observed alterations were indeed due to proteasome inhibition. Two of the most prominently induced genes encoded the growth arrest and DNA damage inducible protein Gadd153 and the activating transcription factor ATF3, both transcription factors of the CCAAT/enhancer binding protein (C/EBP) family. A third gene encoded for the transcriptional repressor and c-Myc antagonist Mad1. Our results suggest that proteasome inhibition leads to upregulation of specific members of transcription factor families controlling cellular stress response and proliferation. Oncogene (2000).

Base Sequence↗

PubMed1999

Gene expression profile of aging and its retardation by caloric restriction.

The gene expression profile of the aging process was analyzed in skeletal muscle of mice. Use of high-density oligonucleotide arrays representing 6347 genes revealed that aging resulted in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes. Most alterations were either completely or partially prevented by caloric restriction, the only intervention known to retard aging in mammals. Transcriptional patterns of calorie-restricted animals suggest that caloric restriction retards the aging process by causing a metabolic shift toward increased protein turnover and decreased macromolecular damage.

Aging↗

PubMed2006

Gene expression profiles underlying alternative caste phenotypes in a highly eusocial bee, Melipona quadrifasciata.

To evaluate caste-biased gene expression in Melipona quadrifasciata, a stingless bee, we generated 1278 ESTs using Representational Difference Analysis. Most annotated sequences were similar to honey bee genes of unknown function. Only few queen-biased sequences had their putative function assigned by sequence comparison, contrasting with the worker-biased ESTs. The expression of six annotated genes connected to caste specificity was validated by real time PCR. Interestingly, queens that were developmentally induced by treatment with a juvenile hormone analogue displayed an expression profile clearly different from natural queens for this set of genes. In summary, this study represents an important first step in applying a comparative genomic approach to queen/worker polyphenism in the bee.

Animals↗

PubMed2006

Gene expression profiles of head and neck carcinomas from Sudanese and Norwegian patients reveal common biological pathways regardless of race and lifestyle.

PURPOSE: To explore possible range of gene expression profiles in head and neck squamous cell carcinomas (HNSCC) and pairwised normal controls from Sudanese (n = 72) and Norwegian (n = 45) patients using a 15K cDNA microarray and to correlate the findings with clinicopathologic variables. EXPERIMENTAL DESIGN: Samples from Sudan were grouped according to anatomic location/patients' habit of toombak (snuff) use, and 37 pools of 2 to 11 tumors matched to 37 pools of their normal controls from the same patients, respectively, were prepared. For Norway, eight pools of 3 to 11 tumors matched to eight pools of their normal controls from the same patients, respectively, were prepared according to anatomic location. Pools (n = 45) were hybridized to microarrays. For controls, 33 of the pools were hybridized against Human Reference RNA. Scanned array images were recorded, and data analysis was done in groups. For verification, results for selected genes were analyzed using quantitative real-time PCR/immunohistochemistry. RESULTS: We identified 136 genes from Sudan and 154 from Norway as differentially expressed between tumors and controls. Changes of the genes found were confirmed in >70% of the pools by hybridization against Reference RNA. Seventy-three genes and three main pathways (signal transduction, cell communication, and ligand-receptor interaction) were of relevance to the HNSCCs from both countries. Hierarchical clustering of the 73 genes identified subclasses of mixed tumors from the two populations, two independent subgroups for Norwegian tumors by their anatomic sites, and five subgroups for Sudanese tumors by their toombak habits. Quantitative real-time PCR/immunohistochemistry validated the microarray-based data. CONCLUSIONS: Differences in gene expression between tumor and nontumor tissues were identified in HNSCCs. Analysis of the two population groups revealed a common set of 73 genes within three main biological pathways. This indicates that the development of HNSCCs is mediated by similar biological pathways regardless of differences related to race, ethnicity, lifestyle, and/or exposure to environmental carcinogens. Of particular interest, however, was the valuable association of gene expression signature found with toombak use and anatomic site of the tumors.

Aged↗

PubMed2005

Molecular changes from dysplastic nodule to hepatocellular carcinoma through gene expression profiling.

Progression of hepatocellular carcinoma (HCC) is a stepwise process that proceeds from pre-neoplastic lesions--including low-grade dysplastic nodules (LGDNs) and high-grade dysplastic nodules (HGDNs)--to advanced HCC. The molecular changes associated with this progression are unclear, however, and the morphological cues thought to distinguish pre-neoplastic lesions from well-differentiated HCC are not universally accepted. To understand the multistep process of hepato-carcinogenesis at the molecular level, we used oligo-nucleotide microarrays to investigate the transcription profiles of 50 hepatocellular nodular lesions ranging from LGDNs to primary HCC (Edmondson grades 1-3). We demonstrated that gene expression profiles can discriminate not only between dysplastic nodules and overt carcinoma but also between different histological grades of HCC via unsupervised hierarchical clustering with 10,376 genes. We identified 3,084 grade-associated genes, correlated with tumor progression, using one-way ANOVA and a one-versus-all unpooled t test. Functional assignment of these genes revealed discrete expression clusters representing grade-dependent biological properties of HCC. Using both diagonal linear discriminant analysis and support vector machines, we identified 240 genes that could accurately classify tumors according to histological grade, especially when attempting to discriminate LGDNs, HGDNs, and grade 1 HCC. In conclusion, a clear molecular demarcation between dysplastic nodules and overt HCC exists. The progression from grade 1 through grade 3 HCC is associated with changes in gene expression consistent with plausible functional consequences.

Carcinoma, Hepatocellular↗

PubMed2003

Altered patterns of gene expression distinguishing ascending aortic aneurysms from abdominal aortic aneurysms: complementary DNA expression profiling in the molecular characterization of aortic disease.

OBJECTIVES: The purpose of this study was to profile altered patterns of gene expression that characterize degenerative ascending thoracic aortic aneurysms and to compare these patterns with those observed for infrarenal abdominal aortic aneurysms. METHODS: Full-thickness aortic wall tissues were obtained during surgical repair of degenerative thoracic aortic aneurysms and infrarenal abdominal aortic aneurysms (n = 4 each), with normal thoracic and abdominal aortas from organ transplant donors used as control preparations. Radiolabeled complementary DNA was prepared for each specimen and hybridized to complementary DNA microarrays, and differential levels of gene expression between aneurysmal and normal aortic tissues at each site were assessed by parametric statistics. RESULTS: Of 1185 genes examined, 112 (9.5%) were differentially expressed (P <.05) between thoracic aortic aneurysms and normal thoracic aorta, with 105 increased and 7 decreased. There were 104 genes (8.8%) differentially expressed between infrarenal abdominal aortic aneurysms and normal abdominal aorta (65 increased and 39 decreased). Quantitative increases in expression for 97 genes were unique to thoracic aortic aneurysms, whereas increases for 61 genes were unique to infrarenal abdominal aortic aneurysms. Although 8 gene products were significantly altered in both thoracic and infrarenal abdominal aortic aneurysms, these changes were directionally concordant for only 4 (matrix metalloproteinase 9/gelatinase B, v-yes-1 oncogene, mitogen-activated protein kinase 9, and intercellular adhesion molecule 1/CD54). Results for 9 genes were independently confirmed by quantitative reverse transcriptase-polymerase chain reaction. CONCLUSIONS: Thoracic aortic aneurysms and infrarenal abdominal aortic aneurysms exhibit distinct patterns of gene expression relative to normal aorta from the same sites, with most alterations being unique to each disease. Degenerative aneurysms arising in different locations are thus characterized by a high degree of molecular heterogeneity, reflecting different pathophysiologic mechanisms.

Adolescent↗

PubMed2003

Identification of molecular subtypes of glioblastoma by gene expression profiling.

Epidermal growth factor receptor (EGFR) overexpression occurs in nearly 50% of cases of glioblastoma (GBM), but its clinical and biological implications are not well understood. We have used Affymetrix high-density oligonucleotide arrays to demonstrate that EGFR-overexpressing GBMs (EGFR+) have a distinct global gene transcriptional profile. We show that the expression of 90 genes can distinguish EGFR+ from EGFR nonexpressing (EGFR-) GBMs, including a number of genes known to act as growth/survival factors for GBMs. We have also uncovered two additional novel molecular subtypes of GBMs, one of which is characterized by coordinate upregulation of contiguous genes on chromosome 12q13-15 and expression of both astrocytic and oligodendroglial genes. These results define distinct molecular subtypes of GBMs that may be important in disease stratification, and in the discovery and assessment of GBM treatment strategies.

Astrocytes↗

PubMed2002

Mechanisms in epithelial plasticity and metastasis: insights from 3D cultures and expression profiling.

Most human tumors are of epithelial origin (carcinomas) and metastases from such tumors lead to >80% of all cancer deaths. In contrast to aberrant control of proliferation, cell cycle, apoptosis, angiogenesis, and lifespan, mechanisms involved in local invasion and metastasis are still insufficiently understood. We will review a set of (often conflicting) in vitro/in vivo data that suggest the existence of several types of epithelial cell plasticity changes towards a fibroblastoid, invasive phenotype, which increasingly emerge as crucial events during metastasis. New cellular models were identified, which form organotypic structures under near-physiological 3D-culture conditions in vitro as well as tumors/metastases in vivo. In these models, key proteins and signaling pathways were identified (e.g., TGFbeta, ERK/MAPK, PI3K, and PDGF), which specify distinct types of epithelial plasticity correlated with steps in cancer progression and metastasis. The existence of several distinct epithelial plasticity phenotypes is also strongly suggested by expression profiling of polysome-bound mRNA, yielding a better representation of the proteome than conventional expression profiling.

Animals↗

PubMed2004

Papillary and follicular thyroid carcinomas show distinctly different microarray expression profiles and can be distinguished by a minimum of five genes.

PURPOSE: We have previously conducted independent microarray expression analyses of the two most common types of nonmedullary thyroid carcinoma, namely papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). In this study, we sought to combine our data sets to shed light on the similarities and differences between these tumor types. MATERIALS AND METHODS: Microarray data from six PTCs, nine FTCs, and 13 normal thyroid samples were normalized to remove interlaboratory variability and then analyzed by unsupervised clustering, t test, and by comparison of absolute and change calls. Expression changes in four genes not previously implicated in thyroid carcinogenesis were verified by reverse transcriptase polymerase chain reaction on these same samples, together with eight additional FTC tumors. RESULTS: PTCs showed two distinct groups of genes that were either over- or underexpressed compared with normal thyroid, whereas the predominant changes in FTCs were of decreased expression. Five genes could collectively distinguish the two tumor types. PTCs showed overexpression of CITED1, claudin-10 (CLDN10), and insulin-like growth factor binding protein 6 (IGFBP6) but showed no change in expression of caveolin-1 (CAV1) or -2 (CAV2); conversely, FTCs did not express CLDN10 and had decreased expression of IGFBP6 and/or CAV1 and CAV2. CONCLUSION: PTC and FTC show distinctive microarray expression profiles, suggesting that either they have different molecular origins or they diverge distinctly from a common origin. Furthermore, if verified in a larger series of tumors, these genes could, in combination with known tumor-specific chromosome translocations, form the basis of a valuable diagnostic tool.

Adenocarcinoma, Follicular↗

PubMed2006

Gene-expression profiling of HIV-1 infection and perinatal transmission in Botswana.

Perinatal transmission of human immunodeficiency virus (HIV)-1 represents a major problem in many regions of the world, especially Southern Africa. With the exception of viral and proviral load, the role for maternal cofactors in perinatal transmission outcome is largely unknown. In this study, an assessment was made of peripheral blood mononuclear cells (PBMC) gene-expression profiles to better understand transcriptional changes associated with HIV-1 infection and perinatal transmission among young adult mothers with infants in Botswana. Peripheral blood mononuclear cells specimens were used from 25 HIV+ drug naive and 20 HIV- healthy mothers, similar in age and location, collected in 1999-2000 and 2003, and processed with the exact same methods, as previously described. Expression profiling of 22 277 microarray gene probes implicated a broad initiation of innate response gene-sets, including toll-like receptor, interferon-stimulated and antiviral RNA response pathways in association with maternal HIV-1 infection. Maternal transmission status was further associated with host genes that influence RNA processing and splicing patterns. In addition to real-time polymerase chain reaction validation of specific genes, enriched category validation of PBMC profiles was conducted using two independent data sets for either HIV-1 infection or an unrelated RNA virus, severe acute respiratory virus infection. HIV-1 pathogen-specific host profiles should prove a useful tool in infection and transmission intervention efforts worldwide.

Adolescent↗

PubMed2005

Expression profiling using human tissues in combination with RNA amplification and microarray analysis: assessment of Langerhans cell histiocytosis.

Advances in molecular genetics have led to sequencing of the human genome, and expression data is becoming available for many diverse tissues throughout the body, allowing for exciting hypothesis testing of critical concepts such as development, differentiation, homeostasis, and ultimately, disease pathogenesis. At present, an optimal methodology to assess gene expression is to evaluate single cells, either identified physiologically in living preparations, or by immunocytochemical or histochemical procedures in fixed cells in vitro or in vivo. Unfortunately, the quantity of RNA harvested from a single cell is not sufficient for standard RNA extraction methods. Therefore, exponential polymerase-chain reaction (PCR) based analyses, and linear RNA amplification including amplified antisense (aRNA) RNA amplification and a newly developed terminal continuation (TC) RNA amplification methodology have been used in combination with microdissection procedures such as laser capture microdissection (LCM) to enable the use of microarray platforms within individual populations of cells obtained from a variety of human tissue sources such as biopsy-derived samples {including Langerhans cell histiocytosis (LCH)} as well as postmortem brain samples for high throughput expression profiling and related downstream genetic analyses.

Gene Expression Profiling↗

PubMed2001

Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver.

Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive HCC through the generation of a large set of 5'-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes/ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC/noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-beta-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.

Carcinoma, Hepatocellular↗