Mitochondria have been implicated in insulin resistance and beta cell dysfunction, both of which comprise the core pathophysiology of type 2 diabetes mellitus (T2DM). It has also recently been found that mtDNA haplogroups are distinctively associated with susceptibility to T2DM at least in Koreans and Japanese.
Gene expression pattern in transmitochondrial cytoplasmic hybrid cells harboring type 2 diabetes-associated mitochondrial DNA haplogroups.
Specimen part
View SamplesThis study aimed to identify the genetic signatures associated with disease prognosis in bladder cancer. We used 165 primary bladder cancer samples, 23 recurrent non-muscle invasive tumor tissues, 58 normal looking bladder mucosae surrounding cancer and 10 normal bladder mucosae for microarray analysis. Hierarchical clustering was used to stratify the prognosis-related gene classifiers. For validation, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) of top-ranked 14 genes was performed. On unsupervised hierarchical clustering using prognosis related gene-classifier, tumors were divided into 2 groups. The high risk gene signatures had significantly poor prognosis compared to low risk gene signatures (P<0.001 by the log-rank test, respectively). The prognosis-related gene classifiers correlated significantly with recurrence of non-muscle invasive bladder cancer (hazard ratio, 4.09; 95% confidence interval [CI], 1.94 to 8.64; P<0.001), and progression (hazard ratio, 23.68; 95% confidence interval [CI], 4.91 to 114.30; P<0.001), cancer-specific survival (hazard ratio, 29.25; 95% confidence interval [CI], 3.47 to 246.98; P=0.002) and overall survival (hazard ratio, 23.33; 95% confidence interval [CI], 4.97 to 109.50; P<0.001) of muscle invasive bladder cancer (p < 0.001, respectively). No patient with non-muscle invasive bladder cancer experienced cancer progression in low risk gene signature group. Prognosis-related gene classifiers validated by RT- PCR showed identical results. Prognosis related gene-classifiers provided strong predictive value for disease outcome. These gene classifiers could assist in selecting patients who might benefit from more aggressive therapeutic intervention or surveillance.
Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer.
Sex, Age, Specimen part, Disease stage
View SamplesGene expression data from 100 human hepatocellular carcinomas (HCC) were generated and analyzed as part of effort for validating prognostic gene expression signatures from previous studies. Using four different classification algorithms and leave-one-out cross-validation approaches, four different prognostic signatures were applied to test the robustness and concordance of predicted outcome in individual patients. All four tumor-derived signatures were significantly associated with prognosis and had a high rate of concordance with predicted outcomes for individual patients.
Sixty-five gene-based risk score classifier predicts overall survival in hepatocellular carcinoma.
No sample metadata fields
View SamplesCholangiocarcinoma (CC) is an aggressive tumor that shows a poor survival rate even after resection. The present study aimed at identification of the genome-wide expressed genes related to CC oncogenesis and its sarcomatous transdifferentiation using DNA microarray technology. The differentially expressed genes in 9 cholangiocarcinoma cell lines (Choi.CK, Cho.CK, J.CK, S.CK, CK.L1, CK.L2, CK.P1, CK.P2 and CK.Y1) were analyzed in comparison with 4 kinds of cultured biliary epithelial cells (ND.1, ND.2, ND.3 and ND.4) using the Illumina Human-6 v2 BeadChip (48 K). Unsupervised hierachical clustering analysis perfectively classified the 13 cell samples into two groups, normal biliary epithelial (N) and immortalized biliary epithelial cells and CC (T) cells. We identified 120 commonly upregulated ( > 2.5 fold) genes and 340 commonly downregulated ( < 0.4-fold) genes in the two groups. Hierachical clustering analysis of sarcomatoid CC cells (S.CK) revealed 316 differentially upregulated genes (> 4-fold) and 335 downregulated genes (< 0.25-fold).) compared with 3 CC cell lines (Choi.CK, Cho.CK, and J.CK). In conclusion, these data will contribute to better understand the molecular mechanisms of oncogenesis and transdifferentiation in CC and provide the molecular targets for CC diagnosis and therapy.
Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma.
Specimen part, Cell line, Treatment
View SamplesFull title: Predictive Gene Signatures as Strong Prognostic Indicators of the Effectiveness of Bacillus CalmetteGurin (BCG) Immunotherapy in Primary pT1 Bladder Cancers
Gene signatures for the prediction of response to Bacillus Calmette-Guerin immunotherapy in primary pT1 bladder cancers.
Sex, Age, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
HOXA9, ISL1 and ALDH1A3 methylation patterns as prognostic markers for nonmuscle invasive bladder cancer: array-based DNA methylation and expression profiling.
Sex, Age, Specimen part, Disease stage
View SamplesThe DNA methylation patterns associated with the development and progression of cancer. The aim of the present study was to identify novel methylation markers that can discriminate between normal and Non-muscle-invasive bladder cancer (NMIBC), and between good and poor prognosis using microarray analysis of DNA methylation and RNA expression patterns in NMIBC patients. From the 24 matched microarray-based DNA methylation and gene expression profiling data set, tumor specific hypermethylated genes were selected and clinical relevance of these genes were verified by quantitative PQS analyses. Methylation statues of several genes were significantly associated with decreased gene expression levels and aggressive clinicopathological characteristics. In multivariate regression analyses, hypermethylation of these genes were the independent predictors of recurrence and progression.
HOXA9, ISL1 and ALDH1A3 methylation patterns as prognostic markers for nonmuscle invasive bladder cancer: array-based DNA methylation and expression profiling.
Sex, Age, Specimen part, Disease stage
View SamplesTo investigate the in vivo developmental potential, we generated dedifferentiated-skin fibroblast from adult skin fibroblasts with a FVB background, a different genetic strain from the protein-donor embryonic stem (ES) cell. Primary cardiac fibroblast (cFB) was cultered from an adult C57/BL mouse to compare with ES cells(E14-mES, C57-mES). We also introduced C57 background ES cell-derived extract proteins into cFB by reversible permeabilisation. The ES-like cells (colonies) were expanded with subculture every 3 to 5 days using the standard ES cell culture protocol.
No associated publication
Specimen part
View SamplesEx-vivo expanded mesenchymal stromal cells (MSCs) are increasingly used for paracrine support of hematopoietic stem cell (HSC) regeneration, but inconsistent outcomes have been the huddle for on-going clinical trials. Here, we hypothesized that the heterogeneity in the niche activity of manufactured MSCs can be a parameter for variable outcomes in MSC-based cell therapy. We first screened MSC culture medium and found that serum batches caused larger variations in colony forming unit-fibroblast (CFU-F) content of MSCs than individual donor variations. The culture conditions supporting high (stimulatory) and low (non-stimulatory) CFU-F caused distinct niche activity of MSCs; MSCs under stimulatory condition exhibited higher level expression of cross-talk molecules (Jagged-1 and CXCL-12) and higher support for HSCS during long-term culture than MSCs under non-stimulatory culture. Moreover, the effects of MSCs enhancing hematopoietic engraftment were only visible when HSCs were co-transplanted with MSCs expanded under stimulatory, but not non-stimulatory conditions. However, these differences of MSCs were readily reversed by switching the culture mediums, indicating their distinct functional state, rather than clonal heterogeneity. Accordingly, transcriptomic analysis showed distinct gene set enrichment between the different MSCs and revealed distinct upstream signaling pathways such as inhibition of P53 and activation of ATF4 for MSCs under stimulatory conditions. Taken together, our study shows that the heterogeneity in the niche activity of MSCs can be created during ex-vivo expansion to cause a difference in the hematopoietic engraftment and raise the possibility that MSCs can be pre-screened for more predictable outcomes in clinical trials of MSCs.
No associated publication
Sex, Age, Specimen part, Cell line
View SamplesMicroarray-based DNA methylation and gene expression profiling was carried out using a panel of prostate cancer cell lines (LNCaP-FGC, DU-145, and PC-3) and the control normal prostate RWPE1 cell line. The identification of prostate cancer-specific methylation markers was based on the following criteria: a difference in DNA methylation level () of at least 0.5, and at least a 2-fold difference in expression level between cancer and control cells. Using highly stringent selection criteria, we identified novel hypermethylated genes whose expression was silenced in prostate cancer cells.
EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling.
Specimen part, Cell line
View Samples