We performed expression profiling of 36 types of normal human tissues and identified 2,503 tissue-specific genes. We then systematically studied the expression of these genes in cancers by re-analyzing a large collection of published DNA microarray datasets. Our study shows that integration of each gene's breadth of expression (BOE) in normal tissues is important for biological interpretation of the expression profiles of cancers in terms of tumor differentiation, cell lineage and metastasis.
Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues.
No sample metadata fields
View SamplesThe aim of this study is to identify responders to FOLFOX therapy by applying the Random Forests (RF) algorithm to gene expression data. Eighty-three unresectable colorectal cancer (CRC) patients including 42 responders and 41 non-responders were divided into training (54 patients) and test (29 patients) sets.
Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis.
Sex
View SamplesChronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) appear to be the most significant causes of hepatocellular carcinoma (HCC). Aberrant promoter methylation is known to be deeply involved in cancer, including HCC. In this study, we analyzed aberrant promoter methylation on genome-wide scale in 6 HCCs including 3 HBV-related and 3 HCV-related HCCs, 6 matched noncancerous liver tissues and 3 normal liver tissues by methylated DNA immunoprecipitation-on-chip analysis. Candidate genes with promoter methylation were detected more frequently in HCV-related HCC. Candidate genes methylated preferentially to HBV-related or HCV-related HCCs were detected and selected, and methylation levels of the selected genes were validated using 125 liver tissue samples, including 61 HCCs (28 HBV-related HCCs and 33 HCV-related HCCs) and matched 59 matched noncancerous livers, and 5 normal livers, by quantitative methylation analysis using MALDI-TOF mass spectrometry. Among analyzed genes, preferential methylation in HBV-related HCC was validated in 1 gene only. However, 15 genes were found methylated preferentially in HCV-related HCC, which was independent from age. Hierarchical clustering of HCC using these 15 genes stratified HCV-related HCC as a cluster of frequently methylated samples. The 15 genes included genes inhibitory to cancer-related signaling such as RAS/RAF/ERK and Wnt/b-catenin pathways. It was indicated that genes methylated preferentially in HCV-related HCC exist, and it was suggested that DNA methylation might play an important role in HCV-related HCC by silencing cancer-related pathway inhibitors.
Identification of genes preferentially methylated in hepatitis C virus-related hepatocellular carcinoma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesAberrant DNA methylation, one of the major epigenetic alterations in cancer, has been reported to accumulate in a subset of colorectal cancer (CRC), so-called CpG island methylator phenotype (CIMP), which was known to correlate with microsatellite instability (MSI)-high CRC. To select new methylation markers genome-widely and epigenotype CRC by DNA methylation comprehensively, we performed methylated DNA immunoprecipitation-on-chip analysis using MSI-high CRC cell line HCT116 and microsatellite-stable SW480, and re-expression array analysis by 5-aza-2-deoxycytidine/Trichostatin A. Methylation levels of 44 new markers selected and 16 previously reported markers were analyzed quantitatively in 149 clinical CRC samples using MALDI-TOF mass spectrometry. By unsupervised two-way hierarchical clustering, CRC was clustered into high-, intermediate-, and low-methylation epigenotypes. Methylation markers were clustered into two groups: Group-1 showing methylation in high-methylation epigenotype and including all the 11 CIMP-related markers except NEUROG1, and Group-2 showing methylation in high- and intermediate-methylation epigenotypes. Marker panel deciding methylation epigenotypes with the highest accuracy was developed: 1st-Panel consisting of Group-1 genes (CACNA1G, LOX, SLC30A10) to extract high-methylation epigenotype, and 2nd-Panel consisting of Group-2 genes (ELMO1, FBN2, THBD, HAND1) and SLC30A10 again to divide the remains into intermediate- and low-methylation epigenotypes. High-methylation epigenotype correlated significantly with BRAF mutation, MSI, proximal tumor location, and mucinous component, in concordance with reported CIMP. Intermediate- and low-methylation epigenotypes significantly correlated with KRAS-mutation(+) and KRAS-mutation(-), respectively. KRAS-mutation(+) intermediate-methylation epigenotype showed worse prognosis than KRAS-mutation(-) low-methylation epigenotype (p=0.030). These three epigenotypes with different genetic characteristics suggested different molecular CRC genesis, and the markers might be useful to predict prognosis.
Three DNA methylation epigenotypes in human colorectal cancer.
Specimen part, Cell line
View SamplesGlioma initiating cells (GICs) are considered responsible for the therapeutic resistance and recurrence of malignant glioma. To clarify the molecular mechanism of GIC maintenance/differentiation, we established GIC clones from GBM patient tumors having the potential to differentiate into malignant gliomas in mouse intracranial xenograft, and established an in vitro glioma induction system by using serum stimulation.
Glioma initiating cells form a differentiation niche via the induction of extracellular matrices and integrin αV.
No sample metadata fields
View SamplesThe Golgi stress response is a homeostatic mechanism that augments the functional capacity of the Golgi apparatus when Golgi function becomes insufficient (Golgi stress). Three response pathways of the Golgi stress response have been identified in mammalian cells, the TFE3, HSP47 and CREB3 pathways, which augment the capacity of specific Golgi functions such as N-glycosylation, anti-apoptotic activity and pro-apoptotic activity, respectively. On the contrary, glycosylation of proteoglycans (PGs) is another important function of the Golgi, although the response pathway upregulating expression of glycosylation enzymes for PGs in response to Golgi stress remains unknown. Here, we found that expression of glycosylation enzymes for PGs was induced upon insufficiency of PG glycosylation capacity in the Golgi (PG-Golgi stress), and that transcriptional induction of genes encoding glycosylation enzymes for PGs was independent of the known Golgi stress response pathways and ER stress response. Promoter analyses of genes encoding these glycosylation enzymes revealed the novel enhancer element PGSE, which regulates their transcriptional induction upon PG-Golgi stress. From these observations, the response pathway we discovered is a novel Golgi stress response pathway, which we have named the PG pathway. Overall design: Three control samples (DMSO-treated) and three 4MU-xyloside-treated samples
PGSE Is a Novel Enhancer Regulating the Proteoglycan Pathway of the Mammalian Golgi Stress Response.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Effects of Acute Prenatal Exposure to Ethanol on microRNA Expression are Ameliorated by Social Enrichment.
Sex
View SamplesIn this study, we tested if miRNAs are altered in amygdala and ventral striatum as a consequence of prenatal ethanol exposure and/or social enrichment. miRNA samples from 72 male and female adolescent rats were analyzed by RNA-Seq analysis and Affymetrix miRNA arrays. Several miRNAs showed significant changes due to prenatal ethanol exposure or social enrichment in one or both brain regions. Some of the miRNA changes caused by ethanol were reversed by social enrichment. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. We also directly examined the evidence for modulation of target mRNAs in whole transcriptome microarray data from the same rats. Among the pathways most strongly affected were p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for social enrichment to reverse the effects of ethanol exposure.
Effects of Acute Prenatal Exposure to Ethanol on microRNA Expression are Ameliorated by Social Enrichment.
Sex
View SamplesTo compare the RNAs present in dendrites and somas of individual neurons, we manually separated the dendrites and soma of primary mouse hippocampal neurons using a micropipette and performed RNA-sequencing on each subcellular fraction such that we obtained the subcellular transcriptomes of the same cell. Overall design: 16 individual neurons were collected and dissected (yielding a total of 32 soma and dendrite samples) from multiple cultures across multiple days. ERCC spike-in control RNA was added to each sample.
Comprehensive catalog of dendritically localized mRNA isoforms from sub-cellular sequencing of single mouse neurons.
Cell line, Subject
View SamplesAnalysis of expression changes in prelabeled laser-microdissected thoracic propriospinal neurons at different times after low-thoracic spinal cord transection in adult rats.
Intrinsic response of thoracic propriospinal neurons to axotomy.
Sex, Age, Specimen part, Time
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