4 chorionic villus sampling specimens in pregnancies destined for preeclampsia and 8 matched controls were analyzed
Altered global gene expression in first trimester placentas of women destined to develop preeclampsia.
No sample metadata fields
View SamplesBackground: Local recurrence is the major manifestation of treatment failure in patients with operable laryngeal carcinoma. Established clinicopathological factors cannot sufficiently predict patients that are likely to recur after treatment. Additional tools are therefore required to accurately identify patients at high risk for recurrence. Methods: Using Affymetrix U133A Genechips, we profiled fresh-frozen tumor tissues from 59 patients with operable laryngeal cancer. All patients were treated locally with surgery, with or without radiation therapy. We performed Cox regression proportional hazards modeling to identify multigene predictors of recurrence. The end-point of our analysis was disease-free survival (DFS). Gene models were directly validated in a separate, similarly treated cohort of 50 patients using Affymetrix chips. In an attempt to further validate our results, we profiled 12 selected genes of our model in formalin-fixed tumor tissues from an independent cohort of 75 patients, using quantitative real time-polymerase chain reaction (qRT-PCR). Results: We focused on genes univariately associated with DFS (p<0.05) in the training set. Among several gene models comprising different numbers of genes, a 30-gene model demonstrated optimal performance (log-rank, p<0.001). We directly applied these gene models to the validation set, after adjusting for non-biological experimental variability, and observed similar results. Specifically, median DFS, as predicted by the 30-gene model, was 34 and 80 months for high- and low-risk patients, respectively (p=0.01). Hazard Ratio (HR) for recurrence for the high-risk group was 3.87 (95% CI 1.28-11.73, p=0.017). Furthermore, unsupervised hierarchical clustering of the 75 patients, based on the qRT-PCR 12-gene profile, yielded two groups, which differed significantly in DFS (log-rank, p=0.027). HR= for recurrence was 2.26, (95% CI 1.08-4.76, p=0.031). Conclusion: We have established and validated gene models that can successfully stratify patients with laryngeal cancer, based on their risk for recurrence. Thus, patients with unfavorable prognosis, when accurately identified, could be ideal candidates for the application of more aggressive treatment modalities.
Identification and validation of a multigene predictor of recurrence in primary laryngeal cancer.
Age, Specimen part, Disease stage
View SamplesRANK-positive and RANK-negative luminal progenitor cells were isolated by FACS from histologically normal human breast tissue from wild-type human donors. RNA-seq gene expression profiling was used to find differentially expressed genes between the RANK-positive and RANK-negative cell populations. Overall design: Cells were isolated from 4 human patients. A paired analysis was used to compare RANK-positive and RANK-negative cells within patients.
RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.
No sample metadata fields
View SamplesBRCA1, a well-known breast and ovarian cancer susceptibility gene with multiple interacting partners, is predicted to have diverse biological functions. However, to date its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate risk variant, and found that it does not impair DNA damage repair but abrogates the repression of miR-155, a bona fide oncomir. We further show that in the absence of functional BRCA1, miR-155 is up-regulated in BRCA1-deficient mouse mammary epithelial cells, human and mouse BRCA1-deficienct breast tumor cell lines as well as tumors. Mechanistically, we found that BRCA1 represses miR-155 expression via its association with HDAC2, which deacetylates H2A and H3 on the miR-155 promoter. Finally, we show that over-expression of miR-155 accelerates whereas the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Taken together, our findings demonstrate a new mode of tumor suppression by BRCA1 and reveal miR-155 as a potential therapeutic target for BRCA1-deficient tumors.
Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155.
Specimen part
View SamplesWe examined the functional significance of the R1699Q variant of human BRCA1 gene using a mouse ES cell-based assay.
Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155.
Specimen part
View SamplesWe performed a time-course microarray experiment to define the transcriptional response to carboplatin in vitro, and to correlate this with clinical outcome in epithelial ovarian cancer (EOC). RNA was isolated from carboplatin and control-treated 36M2 ovarian cancer cells at several time points, followed by oligonucleotide microarray hybridization. Carboplatin induced changes in gene expression were assessed at the single gene as well as at the pathway level. Clinical validation was performed in publicly available microarray datasets using disease free and overall survival endpoints.
Carboplatin-induced gene expression changes in vitro are prognostic of survival in epithelial ovarian cancer.
No sample metadata fields
View SamplesA gene expression profile of BRCAness was defined in publicly available expression data of 61 patients with epithelial ovarian cancer (34 patients with BRCA-1 or BRCA-2 mutations and 27 patients with sporadic disease). This dataset is publicly available at http://jnci.oxfordjournals.org/cgi/content/full/94/13/990/DC1
Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer.
Age, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers.
Disease, Disease stage, Cell line
View SamplesA variety of human cancers demonstrate alterations in microRNA expression. We hypothesized that regulatory defects in microRNAs play a central early role in organizing the molecular changes involved in ovarian cancer (OvCa). Using both gene arrays and deep sequencing, we comprehensively profiled mRNA and microRNA expression, respectively, in human serous epithelial OvCa cell lines, serous tumors, and short-term primary cultures of normal ovarian surface epithelium (NOSE). We expected that over-expression of a specific microRNA would lead to lower expression of its mRNA targets, and under-expression of a specific microRNA would lead to higher expression of its target genes. Using our expression data in conjunction with established in silico algorithms, we found putative microRNA:mRNA functional pairs.
Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers.
Disease, Disease stage, Cell line
View SamplesA variety of human cancers demonstrate alterations in microRNA expression. We hypothesized that regulatory defects in microRNAs play a central early role in organizing the molecular changes involved in ovarian cancer (OvCa). Using both gene arrays and deep sequencing, we comprehensively profiled mRNA and microRNA expression, respectively, in human serous epithelial OvCa cell lines, serous tumors, and short-term primary cultures of normal ovarian surface epithelium (NOSE). We expected that over-expression of a specific microRNA would lead to lower expression of its mRNA targets, and under-expression of a specific microRNA would lead to higher expression of its target genes. Using our expression data in conjunction with established in silico algorithms, we found putative microRNA:mRNA functional pairs. Furthermore, gene expression profiles were taken of serous cultures having functional knockdown or over-expression of specific microRNAs of interest. Over-expression of mir-31 (found under-expressed in serous OvCa) resulted in down-regulation in vitro of a significant number of the in silico predicted mir-31 target genes.
Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers.
No sample metadata fields
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