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GSE54388
Homo sapiens
20 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ovarian cancer is the fifth most common form of cancer in women in the United States. Epithelial ovarian cancer is the most common and is highly lethal. In 2014, there will be an estimated 21,980 new cases and 14,270 deaths from ovarian cancer in the United States. No major strides have been made to improve survival over the past decade. Ovarian cancer is notable for initial chemotherapy sensitivity (>75% response rates) using combination platinum and taxane chemotherapy following debulking surgery. However, eventually, the vast majority of these women (>75-80%) will have their cancer recur within 12 to 24 months after diagnosis and will die of progressively chemotherapy-resistant diseases. Transcription factors act as master switches of various biochemical pathways by regulating gene transcription. Large number of studies demonstrated the role of transcription factors in cancer development and progression. However, transcription factors involved in the pathogenesis of ovarian cancer have not been explored thoroughly. Therefore, we propose to using transcriptome profiling to generate a transcription factor gene signature for high-grade serous ovarian cancer.
Publication Title
ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed.
Publication Title
BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. PAX2 promotes cell proliferation, oncogenic transformation, cell lineage specification, migration, and survival. In our previous study, we found that PAX2 is highly expressed in low-grade ovarian serous carcinoma, but its expression in clear cell, endometrioid, and mucinous cell ovarian carcinomas have not been studied. More importantly, the functional role of PAX2 in ovarian cancer is not known.
Publication Title
PAX2 Expression in Ovarian Cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Objective: Ovarian tumors of low-malignant potential (LMP) and low-grade serous ovarian carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from that of high-grade serous ovarian carcinoma. Past studies have utilized gene expression profiles to support this theory. The objective of the current study was to identify new genes whose expression profiles in LMP ovarian tumors and low-grade ovarian carcinomas differ from that in high-grade ovarian carcinomas.
Publication Title
PAX2 expression in low malignant potential ovarian tumors and low-grade ovarian serous carcinomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Low-grade serous ovarian carcinoma is believed to arise from serous borderline ovarian tumors, yet the progression from serous borderline tumors to low-grade serous ovarian carcinoma remains poorly understood. The purpose of this study was to identify differentially expressed genes between the two groups. Expression profiles were generated from 6 human ovarian surface epithelia (HOSE), 8 serous borderline ovarian tumors (SBOT), 13 low-grade serous ovarian carcinomas (LG), and 22 high-grade serous ovarian carcinomas (HG). The anterior gradient homolog 3 (AGR3) gene was found to be highly upregulated in serous borderline ovarian tumors; this finding was validated by real-time quantitative RT-PCR, Western blotting, and immunohistochemistry. Anti-AGR3 immunohistochemistry was performed on an additional 56 LG and 103 HG tissues and the results were correlated with clinical data. Expression profiling determined that 1254 genes were differentially expressed (P < 0.005) between SBOT, LG and HG tumors. Serous borderline ovarian tumors exhibited robust positive staining for AGR3, with a lower percentage of tumor cells stained in LG and HG. Immunofluorescence staining indicated that AGR3 expression was limited to ciliated cells. Tumor samples with a high percentage (>10%) of AGR3 positively stained tumor cells were associated with improved longer median survival in both the LG (P = 0.013) and HG (P = 0.008) serous ovarian carcinoma groups. The progression of serous borderline ovarian tumors to low-grade serous ovarian carcinoma may involve the de-differentiation of ciliated cells. AGR3 could serve as a prognostic marker for survival in patients with low-grade and high-grade serous ovarian carcinomas.
Publication Title
The anterior gradient homolog 3 (AGR3) gene is associated with differentiation and survival in ovarian cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
We sought to compare mRNA expression profiles between the parental SKOV3ip1 and taxane-resistant SKOV3TRip2 in order to determine what genes are mediating taxane resistance
Publication Title
Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The molecular etiology of invididual differences in complex behavior traits and susceptibility to psychiatric illness remains incomplete. Using an unbiased genetic approach in a mouse model, Quantitative Trait Loci (QTL) influencing anxiety-like behaviors and beta-carboline-induced seizure vulnerability have been mapped to the distal portion of mouse chromosome 10 and an interval specific congenic strain (ISCS; A.B6chr10; 66 cM to telomere) was developed. This A.B6chr10 strain facilitated defining the behavioral influences of this region as well as gene expression profiling to identify candidate gene(s) underlying this QTL. By microarray studies, an unsuspected E3 Ubiquitin Ligase, Ring Finger 41 (Rnf41 / Neuregulin Receptor Degrading Protein1; Nrdp1) was differentially expressed in the region of interest, comparing the hippocampi of A/J vs A.B6chr10 mice as well as A/J vs B6 mice. By RT-PCR, Rnf41 expression levels were significantly increased 1.5 and 1.3-fold in the hippocampi of C57BL6/J and A.B6chr10 mice compared to A/J mice, respectively. In addition, protein levels of Rnf41 were increased in hippocampi of B6 mice compared to A/J mice across postnatal development with a 5.5-fold difference at P56. Among LxS recombinant inbred mice (N=33), Rnf41 hippocampal mRNA expression levels were significantly correlated with open field behavior (r= .454, p=.0073). Re-analyzing a microarray database of human post-mortem prefrontal cortex (Brodmanns Area 46/10), RNF41 mRNA expression levels were reduced significantly in patients with major depression and bipolar disorder compared to unaffected controls. Overall, Rnf41 is a pleiotropic candidate gene for anxiety-like behaviors, depression, and vulnerability to seizures. RNF41 and its binding partners provide novel etiological pathways for influencing behavior, highlighting a potential role for the ubiquitin proteasome system in psychiatric illness.
Publication Title
An E3 ubiquitin ligase, Really Interesting New Gene (RING) Finger 41, is a candidate gene for anxiety-like behavior and beta-carboline-induced seizures.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Macrophages are a heterogeneous cell type implicated in injury, repair, and fibrosis after AKI, but the macrophage population associated with each phase is unclear.results of this study in a renal ischemia-reperfusion injury model allow phenotype and function to be assigned to CD11b+/Ly6C+ monocyte/macrophage populations in the pathophysiology of disease after AKI.
Publication Title
Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Cerebellar development requires regulated proliferation of cerebellar granule neuron progenitors (CGNPs). Inadequate CGNP proliferation causes cerebellar hypoplasia while excessive CGNP proliferation can cause medulloblastoma, the most common malignant pediatric brain tumor. Although Sonic Hedgehog (SHH) signaling is known to activate CGNP proliferation, the mechanisms down-regulating proliferation are less defined. We investigated CGNP regulation by GSK-3, which down-regulates proliferation in the forebrain, gut and breast by suppressing mitogenic WNT signaling. In striking contrast, we found that co-deleting Gsk-3α and Gsk-3β blocked CGNP proliferation, causing severe cerebellar hypoplasia. Transcriptomic analysis showed activated WNT signaling and up-regulated Cdkn1a in Gsk-3-deleted CGNPs. These data show that a GSK-3/WNT axis modulates the developmental proliferation of CGNPs and the pathologic growth of SHH-driven medulloblastoma. The requirement for GSK-3 in SHH-driven proliferation suggests that GSK-3 may be targeted for SHH-driven medulloblastoma therapy.
Publication Title
GSK-3 modulates SHH-driven proliferation in postnatal cerebellar neurogenesis and medulloblastoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Substantial experimental evidence has shown that dedifferentiation from an epithelial state to a mesenchymal-like state (EMT) drives tumor cell metastasis. This transition facilitates tumor cells to acquire motility and invasive features. Intriguingly, tumor cells at the metastatic site are primarily epithelial, and it is believed that they re-differentiate back to an epithelial state by a process called mesenchymal to epithelial transition (MET). However, there is little in vivo evidence to support the MET process.
Publication Title
E-cadherin re-expression shows in vivo evidence for mesenchymal to epithelial transition in clonal metastatic breast tumor cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples