Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Biomarker Profiling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 577 records · Page 32Linked to original sources
PubMed2005

Liquid Tissue: proteomic profiling of formalin-fixed tissues.

Identification and quantitation of candidate biomarker proteins in large numbers of individual tissues is required to validate specific proteins, or panels of proteins, for clinical use as diagnostic, prognostic, toxicological, or therapeutic markers. Mass spectrometry (MS) provides an exciting analytical methodology for this purpose. Liquid Tissue MS protein preparation allows researchers to utilize the vast, already existing, collections offormalin-fixed paraffin-embedded (FFPE) tissues for the procurement of peptides and the analysis across a variety of MS platforms.

Chromatography, Liquid↗
PubMed2003

Gene expression profiling identifies tumour markers potentially playing a role in uveal melanoma development.

Microarray is a powerful tool to compare the gene expression of different tumour specimens and cell lines simultaneously and quantitatively. To get a better insight into genes that are involved in uveal melanoma tumorigenesis, we compared the gene expression profiles of 12 different uveal melanoma cell lines with three melanocyte cell cultures obtained from healthy donor eyes. Gene expression profiles were obtained by nylon filter arrays, containing 1176 gene spots related to cancer development. The expression levels of selected genes were validated on cell lines and primary uveal melanomas by real time RT-PCR, and were subsequently included in cluster analysis. Four candidate tumour markers, Laminin Receptor 1, Endothelin 2, Von Hippel Lindau Binding protein 1 and Cullin 2, have been selected from genes that were differentially expressed in the uveal melanoma cell lines compared to the normal uveal melanocytes. In primary uveal melanomas, these four markers could discriminate between two classes of uveal melanoma, which may be indicative of a differential disease process.

Biomarkers, Tumor↗
PubMed2005

Quantitative real-time PCR for cancer detection: the lymphoma case.

Advances in the biologic sciences and technology are providing molecular targets for diagnosis and treatment of cancer. Lymphoma is a group of cancers with diverse clinical courses. Gene profiling opens new possibilities to classify the disease into subtypes and guide a differentiated treatment. Real-time PCR is characterized by high sensitivity, excellent precision and large dynamic range, and has become the method of choice for quantitative gene expression measurements. For accurate gene expression profiling by real-time PCR, several parameters must be considered and carefully validated. These include the use of reference genes and compensation for PCR inhibition in data normalization. Quantification by real-time PCR may be performed as either absolute measurements using an external standard, or as relative measurements, comparing the expression of a reporter gene with that of a presumed constantly expressed reference gene. Sometimes it is possible to compare expression of reporter genes only, which improves the accuracy of prediction. The amount of biologic material required for real-time PCR analysis is much lower than that required for analysis by traditional methods due to the very high sensitivity of PCR. Fine-needle aspirates and even single cells contain enough material for accurate real-time PCR analysis.

Biomarkers, Tumor↗
PubMed2006

Gene expression data analysis in subtypes of ovarian cancer using covariance analysis.

Many studies have used microarray technology to identify the molecular signatures of human cancer, yet the critical features of these often unmanageably large set of signatures remain elusive. We have investigated co-expression pattern in four subtypes of ovarian cancer from 104 cancer patients using covariance analysis, treating each subtype of ovarian cancer as a distinct disease entity. We sought gene pairs that were transcriptionally co-expressed in one or multiple subtypes of ovarian cancer, establishing a high confidence network of 87 genes interconnected by significantly high co-expression links that were observed in at least two subtypes of ovarian cancer. We have shown that certain groups of co-expressed gene pairs are cancer subtype specific, through demonstrating significant differences in co-expression patterns of gene pairs between subtypes of ovarian cancer. In addition, we identified a set of 24 genes that classified patients into specific cancer subtypes with a misclassification error rate of less than 5%. Our findings illustrate how large public microarray gene expression datasets could be exploited for identification of cancer subtype specific molecular signatures, and how to classify cancer patients into specific subtypes of cancer using gene expression profiles.

Biomarkers, Tumor↗
PubMed2005

Germ cell tumors.

PURPOSE OF REVIEW: This review provides an overview of some of the recent pre-clinical and clinical developments in germ cell tumors. RECENT FINDINGS: Recent epidemiological studies highlight the variations in the geographic and ethnic distribution of germ cell tumors and the changing incidence of seminoma versus nonseminoma in the population. Additional studies are continuing to identify risk factors for germ cell tumors. Expression profiling, both at the gene and protein levels, is beginning to identify, at the molecular level, some of the factors associated not only with germ cell pluripotency but also with the different histologic subtypes of germ cell tumors. Work in the area of identifying potentially new serum tumor markers in germ cell tumor, as well as the role of the traditional tumor markers in predicting outcome to therapy is ongoing. Data is emerging on the role of positron emission tomography in evaluating residual lesions in seminoma. Evolving data on chemotherapy, radiation, and surgery further complements and clarifies information on these treatment modalities, and their potential toxicities, in the management of germ cell tumors. SUMMARY: Ongoing preclinical and epidemiological studies highlight the complexities underlying germ cell tumor pathogenesis. With enhanced understanding of some of these processes, treatments, particularly for advanced stages, will continue to evolve.

Biomarkers, Tumor↗
PubMed2005

Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction.

Trans fatty acid intake has been associated with a higher risk of cardiovascular disease. The relation is explained only partially by the adverse effect of these fatty acids on the lipid profile. We examined whether trans fatty acid intake could also affect biomarkers of inflammation and endothelial dysfunction including C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR-2), E-selectin, and soluble cell adhesion molecules (sICAM-1 and sVCAM-1). We conducted a cross-sectional study of 730 women from the Nurses' Health Study I cohort, aged 43-69 y, free of cardiovascular disease, cancer, and diabetes at time of blood draw (1989-1990). Dietary intake was assessed by a validated FFQ in 1986 and 1990. CRP levels were 73% higher among those in the highest quintile of trans fat intake, compared with the lowest quintile. IL-6 levels were 17% higher, sTNFR-2 5%, E-selectin 20%, sICAM-1 10%, and sVCAM-1 levels 10% higher. Trans fatty acid intake was positively related to plasma concentration of CRP (P = 0.009), sTNFR-2 (P = 0.002), E-selectin (P = 0.003), sICAM-1 (P = 0.007), and sVCAM-1 (P = 0.001) in linear regression models after controlling for age, BMI, physical activity, smoking status, alcohol consumption, intake of monounsaturated, polyunsaturated, and saturated fatty acids, and postmenopausal hormone therapy. In conclusion, this study suggests that higher intake of trans fatty acids could adversely affect endothelial function, which might partially explain why the positive relation between trans fat and cardiovascular risk is greater than one would predict based solely on its adverse effects on lipids.

Biomarkers↗
PubMed2004

Identification of genes whose expression patterns differ in benign lymphoid tissue and follicular, mantle cell, and small lymphocytic lymphoma.

Improved methods for diagnosing small B-cell lymphomas (SBCLs) and predicting patient response to therapy are likely to result from the ongoing discovery of molecular markers that better define these malignancies. In this report, we identify 120 genes whose expression patterns differed between reactive lymph node tissue and three types of SBCL: follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Whereas previously published studies have generally analyzed the gene expression profiles of one type of SBCL, work presented in this paper was intended to identify genes that are differentially expressed between three SBCL subtypes. This analysis was performed using mRNA pooled from multiple specimens representing each tissue type. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to validate the differential expression of 23 of these genes. Among the 23 validated genes were cyclin D1 (CCND1) and B-cell CLL/lymphoma 2, which have well-known roles in lymphoma pathogenesis. The remaining 21 genes have no currently established role in lymphoma development. Using qRT-PCR, the expression of CCND1 and seven additional genes was further studied in a panel of individual specimens. Genes identified in this study are of biological interest and represent candidate diagnostic markers.

Biomarkers, Tumor↗
PubMed2005

Testing association of a pathway with survival using gene expression data.

MOTIVATION: A recent surge of interest in survival as the primary clinical endpoint of microarray studies has called for an extension of the Global Test methodology to survival. RESULTS: We present a score test for association of the expression profile of one or more groups of genes with a (possibly censored) survival time. Groups of genes may be pathways, areas of the genome, clusters from a cluster analysis or all genes on a chip. The test allows one to test hypotheses about the influence of these groups of genes on survival directly, without the intermediary of single gene testing. The test is based on the Cox proportional hazards model and is calculated using martingale residuals. It is possible to adjust the test for the presence of covariates. We also present a diagnostic graph to assist in the interpretation of the test result, visualizing the influence of genes. The test is applied to a tumor dataset, revealing pathways from the gene ontology database that are associated with survival of patients. AVAILABILITY: The Global Test for survival has been incorporated into the R-package globaltest (version 3.0), available at http://www.bioconductor.org

Biomarkers, Tumor↗
PubMed2004

Molecular classification of parathyroid neoplasia by gene expression profiling.

The current classification of sporadic parathyroid neoplasia, specifically the distinction of adenoma from multiple gland neoplasia (double adenoma and nonfamilial primary hyperplasia) is problematic and results in a relatively high rate of clinical error. Oligonucleotide microarrays (Affymetrix U133A) were used to evaluate parathyroid samples from 61 patients; 35 adenomas, 10 nonfamilial multiple gland neoplasia, 3 familial primary hyperplasia, 8 renal-induced hyperplasia, and 5 from patients without parathyroid disease (normals). A multiclass comparison using supervised clustering identified distinct gene signatures for each class of parathyroid samples. We developed a predictor model that correctly identified 34 of 35 cases of adenoma, 9 of 10 cases of nonfamilial multiple gland neoplasia, and identified a minimum set of 11 genes for the distinction of adenoma versus multiple gland neoplasia. All methods of unsupervised clustering showed two related but different types of parathyroid adenomas that we have arbitrarily designated as type 1 and type 2 adenomas. Multiple gland parathyroid neoplasia, which represents either synchronous or asynchronous autonomous growth in two, three, or all four parathyroid glands, is a distinct molecular entity and does not represent the molecular pathogenesis of adenoma occurring in multiple glands.

Adenoma↗
PubMed2002

Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men.

The prostate-specific antigen test has been a major factor in increasing awareness and better patient management of prostate cancer (PCA), but its lack of specificity limits its use in diagnosis and makes for poor early detection of PCA. The objective of our studies is to identify better biomarkers for early detection of PCA using protein profiling technologies that can simultaneously resolve and analyze multiple proteins. Evaluating multiple proteins will be essential to establishing signature proteomic patterns that distinguish cancer from noncancer as well as identify all genetic subtypes of the cancer and their biological activity. In this study, we used a protein biochip surface enhanced laser desorption/ionization mass spectrometry approach coupled with an artificial intelligence learning algorithm to differentiate PCA from noncancer cohorts. Surface enhanced laser desorption/ionization mass spectrometry protein profiles of serum from 167 PCA patients, 77 patients with benign prostate hyperplasia, and 82 age-matched unaffected healthy men were used to train and develop a decision tree classification algorithm that used a nine-protein mass pattern that correctly classified 96% of the samples. A blinded test set, separated from the training set by a stratified random sampling before the analysis, was used to determine the sensitivity and specificity of the classification system. A sensitivity of 83%, a specificity of 97%, and a positive predictive value of 96% for the study population and 91% for the general population were obtained when comparing the PCA versus noncancer (benign prostate hyperplasia/healthy men) groups. This high-throughput proteomic classification system will provide a highly accurate and innovative approach for the early detection/diagnosis of PCA.

Aged↗
PubMed2006

Gene expression profile of B 16(F10) murine melanoma cells exposed to hypoxic conditions in vitro.

Hypoxia is an important feature of tumor microenvironment, exerting far-reaching effects on cells and contributing to cancer progression. Previous studies have established substantial differences in hypoxia response between various cell lines. Investigating this phenomenon in melanoma cells contributes to a better understanding of cell lineage-specific hypoxia response and could point out novel hypoxia-regulated genes. We investigated transcriptional activity of B 16(F10) murine melanoma cells cultured for 24 h under hypoxic (nominal 1% O2, 15 samples including controls) and hypoxia-mimicking conditions (cobalt chloride, 100 or 200 microM, 6 samples including controls). Gene expression profiles were analyzed using MG-U74Av2 oligonucleotide microarrays. Data analysis revealed 2541 probesets (FDR <5%) for 1% oxygen experiment and 364 probesets (FDR <5%) for cobalt chloride, which showed differences in expression levels. Analysis of hypoxia-regulated genes (true hypoxia, 1% O2) by stringent Family-Wise Error Rate estimation indicated 454 significantly changed transcripts (p < 0.05). The most upregulated genes were Lgals3, Selenbpl, Nppb (more than ten-fold increase). We observed significant differences in expression levels of genes regulating glycolysis (Pfkp, Hk2, Aldo3, Eno2), apoptosis (Bnip3, Bnip31, Cdknla), transcription (Bhlhb2, Sap30, Atf3, Mxil), angiogenesis (Vegfa, Adm, Anxa2, Ctgf), adhesion (Pkp2, Itga4, Mcam), migration (Cnn2, Tmsb4x), and other processes. Both true hypoxia and hypoxia mimicry induced HIF-1-regulated genes. However, unsupervised analysis (Singular Value Decomposition) revealed distinct differences in gene expression between these two experimental conditions. Contrary to hypoxia, cobalt chloride caused suppression of gene expression rather than stimulation, especially concerning transcripts related to proliferation, immune response, DNA repair, and melanin biosynthesis.

Animals↗
PubMed2006

Microarray analysis of sarcomas.

Microarrays began to be used to study gene expression profiles in the mid-1990s, but it was only after 2000 that serious attempts have been made to apply this technology to investigate sarcomas. Microarray technologies provide a comprehensive survey of active molecular pathways and potential molecular targets for diagnosis and treatment, but are challenging to use because of issues of specimen collection, cost, and complexities in experimental design and data analysis. As a discovery-based technique, microarray analyses are most valuable when framed around specific gaps in our knowledge of tumor etiology and progression, challenges in differential diagnosis, and pressing therapeutic needs. To date, microarray analyses of sarcomas support their division into molecularly defined and molecularly heterogeneous categories, and have provided useful diagnostic markers for entities such as gastrointestinal stromal tumors, synovial sarcoma, and dermatofibrosarcoma protuberans. Signatures predicting outcome and response to therapy have been published for Ewing sarcoma and osteosarcoma, and receptor tyrosine kinase expression patterns have suggested novel therapeutic approaches which may be applied to several types of sarcoma. Nevertheless, results need to be interpreted in the context of histopathology and validated by complementary technologies and/or other research groups.

Biomarkers, Tumor↗
PubMed2006

Interest of major serum protein removal for Surface-Enhanced Laser Desorption/Ionization - Time Of Flight (SELDI-TOF) proteomic blood profiling.

BACKGROUND: Surface-Enhanced Laser Desorption/Ionization - Time Of Flight (SELDI-TOF) has been proposed as new approach for blood biomarker discovery. However, results obtained so far have been often disappointing as this technique still has difficulties to detect low-abundant plasma and serum proteins. RESULTS: We used a serum depletion scheme using chicken antibodies against various abundant proteins to realized a pre-fractionation of serum prior to SELDI-TOF profiling. Depletion of major serum proteins by immunocapture was confirmed by 1D and 2D gel electrophoresis. SELDI-TOF analysis of bound and unbound (depleted) serum fractions revealed that this approach allows the detection of new low abundant protein peaks with satisfactory reproducibility. CONCLUSION: The combination of immunocapture and SELDI-TOF analysis opens new avenues into proteomic profiling for the discovery of blood biomarkers.

Journal Article↗
PubMed2004

Age-associated alteration of gene expression patterns in mouse oocytes.

Decreasing oocyte competence with maternal aging is a major factor in human infertility. To investigate the age-dependent molecular changes in a mouse model, we compared the expression profiles of metaphase II oocytes collected from 5- to 6-week-old mice with those collected from 42- to 45-week-old mice using the NIA 22K 60-mer oligo microarray. Among approximately 11,000 genes whose transcripts were detected in oocytes, about 5% (530) showed statistically significant expression changes, excluding the possibility of global decline in transcript abundance. Consistent with the generally accepted view of aging, the differentially expressed genes included ones involved in mitochondrial function and oxidative stress. However, the expression of other genes involved in chromatin structure, DNA methylation, genome stability and RNA helicases was also altered, suggesting the existence of additional mechanisms for aging. Among the transcripts decreased with aging, we identified and characterized a group of new oocyte-specific genes, members of the human NACHT, leucine-rich repeat and PYD-containing (NALP) gene family. These results have implications for aging research as well as for clinical ooplasmic donation to rejuvenate aging oocytes.

Aging↗
PubMed2006

Gene expression profile of primary gastric cancer: towards the prediction of lymph node status.

BACKGROUND: The identification of gastric tumors associated with a higher risk of lymph node metastasis could help surgeons select patients who may benefit from extended lymph node dissection. The aim of this study was to screen the genome in the search of primary gastric cancer gene expression profiles that might predict lymph node status. METHODS: The gene expression profile was evaluated in frozen tumor samples obtained from 32 patients with primary gastric adenocarcinomas. The array consisted of a duplicated spot panel of 5,541 human genes. To classify node-positive (N+) and node-negative (N-) cases, a logistic regression model was fitted optimizing the Akaike Information Criteria after a stepwise gene selection. The accuracy was evaluated by means of leave-one-out cross validation. RESULTS: All patients underwent radical gastrectomy and extended lymphadenectomy. Of all the cases, 21 were N+ and 11 demonstrated no lymph node involvement (N-). After quality filtering, the analysis of variance selected a set of 136 genes potentially correlated with nodal involvement (P value <.05). Of these 136 genes, 5 were differentially expressed (adjusted P value <.05). After a stepwise gene selection, only three genes (Bik, aurora kinase B, eIF5A2) were retained in the logistic model, which could correctly predict lymph node status in 30 of 32 cases. CONCLUSIONS: If our findings were confirmed, the identified gene pattern might be used to tailor the extent of lymph node dissection on a single patient basis.

Biomarkers, Tumor↗
PubMed2006

uPAR (CD87) as a biocompatibility marker of dialysis membrane.

BACKGROUND/AIMS: Hemodialysis (HD) therapy may lead to functional changes in patient leukocytes. For example, the upregulation of inflammatory cytokines, such as IL-1beta and TNFalpha, has been well characterized. However, these findings do not explain the entire response of leukocytes in HD. In this study, we carried out a comprehensive gene expression analysis in leukocytes treated with various dialysis membranes using DNA microarrays. The identified gene has the potential to be a new marker for testing dialysis membrane biocompatibility. METHODS: Gene expression profiles were compared between a group of leukocytes treated with various dialysis membranes and an untreated group by using DNA microarray analysis. Expression was confirmed by quantitative RT-PCR. The expression of the gene product (leukocyte surface protein) was examined in 20 chronic HD patients by flow cytometry. RESULTS: In addition to the inflammatory cytokines, the urokinase plasminogen activator receptor (uPAR or CD87) gene was induced in leukocytes treated with each dialysis membrane. The extent of induction depended on the membrane's material composition. The expression of the uPAR (CD87) protein on leukocytes was markedly increased in patients undergoing dialysis therapy. The magnitude of uPAR (CD87) protein expression was correlated with clinical findings, i.e., the degree of leukopenia and the expression of adhesion molecules. CONCLUSIONS: The gene and protein expression of uPAR (CD87) depended on the dialysis membrane material and correlated closely with clinical findings. These results suggest that uPAR has the potential to serve as a marker not only for clinical use but also for the development of new dialysis membranes.

Adult↗
PubMed2006

Identification of RASSF1A modulated genes in nasopharyngeal carcinoma.

RASSF1A is a tumor suppressor gene on 3p21.3 frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma (NPC). To identify RASSF1A target genes in NPC, we have investigated the expression profile of the stable RASSF1A transfectants and controls by high-density oligonucleotide array. A total of 57 genes showed differential expression in the RASSF1A-expressing cells. These RASSF1A target genes were involved in multiple cellular regulatory processes such as transcription, signal transduction, cell adhesion and RNA processing. The RASSF1A-modulated expression of eight selected genes with the highest fold changes (ATF5, TCRB, RGS1, activin betaE, HNRPH1, HNRPD, Id2 and CKS2) by RASSF1A was confirmed in both stable and transient transfectants. Compared with the RASSF1A transfectants, an inverse expression pattern of activin betaE, Id2 and ATF5 was shown in the immortalized nasopharyngeal epithelial cells treated with siRNA against RASSF1A. The findings imply that the expression of activin betaE, Id2 and ATF5 was tightly regulated by RASSF1A and may associate with its tumor suppressor function. Strikingly, overexpression of Id2 is common in NPC and RASSF1A-induced repression of Id2 was mediated by the overexpression of activin betaE. The results suggest a novel RASSF1A pathway in which both activin betaE and Id2 are involved.

Biomarkers, Tumor↗
PubMed2006

Multiregional gene expression profiling identifies MRPS6 as a possible candidate gene for Parkinson's disease.

Combining large-scale gene expression approaches and bioinformatics may provide insights into the molecular variability of biological processes underlying neurodegeneration. To identify novel candidate genes and mechanisms, we conducted a multiregional gene expression analysis in postmortem brain. Gene arrays were performed utilizing Affymetrix HG U133 Plus 2.0 gene chips. Brain specimens from 21 different brain regions were taken from Parkinson's disease (PD) (n = 22) and normal aged (n = 23) brain donors. The rationale for conducting a multiregional survey of gene expression changes was based on the assumption that if a gene is changed in more than one brain region, it may be a higher probability candidate gene compared to genes that are changed in a single region. Although no gene was significantly changed in all of the 21 brain regions surveyed, we identified 11 candidate genes whose pattern of expression was regulated in at least 18 out of 21 regions. The expression of a gene encoding the mitochondria ribosomal protein S6 (MRPS6) had the highest combined mean fold change and topped the list of regulated genes. The analysis revealed other genes related to apoptosis, cell signaling, and cell cycle that may be of importance to disease pathophysiology. High throughput gene expression is an emerging technology for molecular target discovery in neurological and psychiatric disorders. The top gene reported here is the nuclear encoded MRPS6, a building block of the human mitoribosome of the oxidative phosphorylation system (OXPHOS). Impairments in mitochondrial OXPHOS have been linked to the pathogenesis of PD.

Adult↗