Currently there is a lack of effective therapies which result in long-term durable response for patients presenting with advanced and metastatic clear cell renal cell carcinoma (ccRCC). This is due in part to a lack of molecular factors which can be targeted pharmacologically. In order to identify novel tumor-specific targets, we performed high throughput gene array analysis screening numerous patient ccRCC tumor tissues across all stages of disease, and compared their gene expression levels to matched normal kidney. Our results identify a number of genes which demonstrate tumor-specific overexpression, and may present as novel targets for therapy.
Neuronal pentraxin 2 supports clear cell renal cell carcinoma by activating the AMPA-selective glutamate receptor-4.
Specimen part
View SamplesCurrently there is a lack of effective therapies which result in long-term durable response for patients presenting with anaplastic thyroid carcinoma (ATC), a very rare and lethal variant of thyroid cancer. ATC is resistant to chemotherapy, radiation, and targeted therapies currently available. In an effort to identify novel tumor-specific therapeutic targets, we performed high throughput gene array analysis screening numerous patient ATC tumor tissues, and compared their gene expression levels to matched and unmatched normal thyroid tissue samples.
Aberrant lipid metabolism in anaplastic thyroid carcinoma reveals stearoyl CoA desaturase 1 as a novel therapeutic target.
Specimen part
View SamplesPresently, there is a deficiency of effective therapies designed to target clear cell renal cell carcinoma (ccRCC), with poor prognosis resulting in patients with advanced disease. Additionally, there is a lack of molecular factors which can be remedially targeted resulting in tumor specific inhibition, and therefore current therapeutic approaches often produce adverse side effects in patients. We identified that Stearoyl-CoA desaturase 1 (SCD1) was consistently overexpressed in patient ccRCC samples, and further investigation of SCD1 as a potential molecular target for ccRCC intervention utilizing a SCD1 inhibitor (A939572) resulted in tumor specific growth inhibition and induction of cell death. In order to understand the mechanism by which the SCD1 inhibitor mediated its anti-tumor effects, we performed gene array analysis and compared expression patterns between treated and untreated samples.
Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma.
Cell line, Treatment
View SamplesEuropean-American individuals of the GENOA cohort participating in the Genetics of Microangiopathic Brain Injury substudy, which investigates the genetic basis of alteration in brain structure detectable by magnetic resonance imaging.
No associated publication
Sex, Age, Specimen part
View SamplesWe used microarrays to identify the variation of basal gene expression level among 287 lymphoblastoid cell lines.
Radiation pharmacogenomics: a genome-wide association approach to identify radiation response biomarkers using human lymphoblastoid cell lines.
Specimen part
View SamplesBackground: Prostate cancer (PC), a complex disease, can be relatively harmless or extremely aggressive. To identify candidate genes involved in causal pathways of aggressive PC, we implemented a systems biology approach by combining differential expression analysis and co-expression network analysis to evaluate transcriptional profiles using lymphoblastoid cell lines from 62 PC patients with aggressive phenotype (Gleason grade > 8) and 63 PC patients with nonaggressive phenotype (Gleason grade < 5). From 13935 mRNA genes and 273 microRNAs tested, we identified significant differences in 1100 mRNAs and 7 microRNAs with false discovery rate < 0.01. We also identified a co-expression module demonstrating significant association with the aggressive phenotype of PC (p=3.67x10-11). The module of interest was characterized by over-representation of cell cycle-related genes (false discovery rate = 3.50x10-50). From this module, we further defined 20 hub genes that were highly connected to other genes. Interestingly, five of the 7 differentially expressed microRNAs have been implicated in cell cycle regulation and two (miR-145 and miR-331-3p) are predicted to target three of the 20 hub genes. Ectopic expression of these two microRNAs reduced expression of target hub genes and subsequently resulted in cell growth inhibition and apoptosis. These results suggest that cell cycle is likely to be a molecular pathway causing aggressive phenotype of PC. Further characterization of cell cycle-related genes (particularly, the hub genes) and miRNAs that regulate these hub genes could facilitate identification of candidate genes responsible for the aggressive phenotype and lead to a better understanding of PC etiology and progression [Cancer Res 2009;69(24):94907].
Gene networks and microRNAs implicated in aggressive prostate cancer.
Cell line
View SamplesDifferential expression analysis comparing healthy volunteers at sea level and after acute exposure to altitude
No associated publication
No sample metadata fields
View SamplesMost human tumors have abnormal numbers of chromosomes, a condition known as aneuploidy. The mitotic checkpoint is an important mechanism that prevents aneuploidy through restraining the activity of the anaphase-promoting complex (APC). USP44 was identified as a key regulator of APC activation that maintains the association of MAD2 with the APC co-activator Cdc20. However, the physiological importance of USP44 and its impact on cancer biology are unknown. Here, we show that USP44 is required to prevent tumors in mice and is frequently down-regulated in human lung cancer. USP44 inhibits chromosome segregation errors independently of its role in the mitotic checkpoint by regulating proper centrosome separation, positioning, and mitotic spindle geometry, functions that require direct binding to the centriole protein, centrin. These data reveal a new role for the ubiquitin system in mitotic spindle regulation and underscore the importance of USP44 in the pathogenesis of human cancer.
USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis.
Sex, Disease, Disease stage
View SamplesBackground: Expression level of many genes shows abundant natural variation in human populations. The variations in gene expression are believed to contribute to phenotypic differences. Emerging evidence has shown that microRNAs (miRNAs) are one of the key regulators of gene expression. However, past studies have focused on the miRNA target genes and use loss- or gain-of-function approach that may not reflect natural association between miRNA and mRNAs. Methodology/Principal Findings: To examine miRNA regulatory effect on global gene expression under endogenous condition, we performed pair-wise correlation coefficient analysis on expression levels of 366 miRNAs and 14,174 messenger RNAs (mRNAs) in 90 immortalized lymphoblastoid cell lines, and observed significant correlations between the two species of RNA transcripts. We identified a total of 7,207 significantly correlated miRNA-mRNA pairs (false discovery rate q <0.01). Of those, 4,085 pairs showed positive correlations while 3,122 pairs showed negative correlations. Gene ontology analyses on the miRNA-correlated genes revealed significant enrichments in several biological pathways related to cell cycle, cell communication and signal transduction. Individually, each of three miRNAs (miR-331, -98 and -33b) demonstrated significant correlation with the genes in cell cycle-related biological processes, which is consistent with important role of miRNAs in cell cycle regulation. Surprisingly, most miRNA-correlated genes were not direct targets predicted by mRNA target prediction program, TargetScan, suggesting indirect endogenous relationship between miRNAs and their correlated mRNAs. Conclusions/Significance: This study demonstrates feasibility of using naturally expressed transcript profiles to identify endogenous correlation between miRNA and miRNA. By applying this genome-wide approach, we have identified thousands of miRNA-correlated genes and revealed potential role of miRNAs in several important cellular functions. The study results along with accompanying data sets will provide a wealth of high-throughput data to further evaluate the miRNA-regulated genes and eventually in phenotypic variations of human populations.
Genome-wide transcriptional profiling reveals microRNA-correlated genes and biological processes in human lymphoblastoid cell lines.
Cell line
View SamplesMultiple myeloma is a relatively common B-cell malignancy that is currently incurable. Certain recurrent genetic abnormalities characteristics of different genetic subtypes have been described. Hyperdiploid myeloma characterized by recurrent trisomies is the most common genetic subtypes. However little is know about it's biology. Another common genetic abnormality is chromosome 13 deletion which is also associated with inferior prognosis. This abnormality is already present at the pre-malignant MGUS stage and is clonally selected with disease progression. Although it is biologically and clinically important the molecular consequence of chromosome 13 deletion is unknown.
Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling.
No sample metadata fields
View Samples