A consensus hypoxia signature in breast cancer
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ABSTRACT:
PROVIDER: PRJNA437670 | ENA |
REPOSITORIES: ENA
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Project description:We exposed a panel of 32 breast cancer cell lines or normal human mammary epithelial cells to 20% or 1% O2 concentration for 24h. Total RNA was extracted from cells using TRIzol (Invitrogen) and treated with DNase I (Ambion). All samples had a RIN value of >9.0 when measured on an Agilent Bioanalyzer. Libraries for RNA-Seq were prepared with KAPA Stranded RNA-Seq Kit. The workflow consisted of mRNA enrichment, cDNA generation, end repair to generate blunt ends, A-tailing, adaptor ligation and 12 cycles of PCR amplification. Unique adaptors were used for each sample in order to multiplex samples into several lanes. Sequencing was performed on Illumina Hiseq 3000/4000 with a 150bp pair-end run. A data quality check was done on Illumina SAV. Demultiplexing was performed with Illumina Bcl2fastq2 v 2.17 program.
2018-12-26 | GSE111653 | GEO
Project description:Purpose. Temporal and local fluctuations in oxygen levels observed within tumors represent stressful conditions requiring adaptive mechanisms that provide tumor cells with phenotypic alterations to survive and proliferate in this hostile environment. The analysis of the transcriptome associated with such cycling hypoxia could thus represent a prognostic biomarker of cancer progression. Patients and Methods. We exposed 20 cell lines derived from various tissues to repeated periods of hypoxia/reoxygenation in order to determine a transcriptomic signature of cycling hypoxia (CycHyp). We then used clinical data sets from 2,150 patients with primary breast cancer to estimate a prognostic Cox proportional hazard model and to assess the prognostic performance of the CycHyp signature on independent samples. Results. The prognostic potential of the CycHyp signature was validated in patients independently of the receptor status of the tumors (HR=1.97; p = 1.8e-12). The discriminating capacity of the CycHyp signature was further increased in the ER+ HER2- patient populations (HR = 2.34, p = 9e-12) including those with a node negative status receiving or not a treatment (HR = 3.32 and 5.51; p= 5.61e-10 and 8.15e-11, respectively). We also documented the capacity of the CycHyp signature to outperform existing prognostic gene signatures with significantly higher BCR and concordance index. We also showed that the CycHyp signature could identify ER-positive node-negative breast cancer patients at high risk based on conventional clinico-pathologic criteria but who could have been spared from chemotherapy and inversely those patients classified at low risk based on the same criteria but who presented a negative outcome. Conclusion. This study demonstrates that a gene signature derived from the transcriptomic adaptation of tumor cells to cycling hypoxia is prognostic of breast cancer and offers a unique decision making tool to complement the discrimination of breast cancer patients based on anatomo-pathological evaluation. The prognostic value of CycHyp further confirms the link between cycling hypoxia and cancer progression, and thereby paves the way for a broad applicability to evaluate cancer patient outcomes.
2015-11-16 | GSE42416 | GEO
Project description:Hypoxia is an important driver of cancer progression, and rapidly growing tumors often result in intratumoral hypoxic regions. Hypoxia is associated with metabolic reprogramming and angiogenesis, resulting in enhanced tumor progression. Here, we aimed to study breast cancer hypoxia responses at the proteomic level, and we wanted to identify differences in protein secretion from luminal-like and basal-like cell lines before and after hypoxia.
2023-06-23 | PXD027136 | Pride
Project description:The ER alpha positive breast cancer MCF7 cells were treated with ER alpha antagonist ICI182780 in normoxia and hypoxia. Extracted RNA was subject to microarray analysis. The goal of the experiment is to assess the ICI182780 effect on breast cancer cell in both normoxia and hypoxia.
2015-10-01 | GSE61799 | GEO
Project description:Analysis of transcriptome post hypoxia and TGF-β treatment in breast cancer In order to explore the role of TGF-β signaling in mediating the alternative splicing program in breast cancer, we profiled the pre-mRNA splicing and mRNA gene expression upon hypoxia and TGF-β treatment using Human Transcriptome Array 2.0.
2020-08-24 | GSE147516 | GEO
Project description:Dysregulated Notch signalling contributes to breast cancer development and progression, but validated tools to measure the level of Notch signalling in breast cancer subtypes and in response to systemic therapy are largely lacking. A transcriptomic signature of Notch signalling would thus be warranted, and in this report, we have established such a classifier. To generate the signature, we first identified Notch-regulated genes from six basal-like breast cancer cell lines subjected to elevated and reduced Notch signalling by culturing on immobilized Notch ligand Jagged1 or blockade of Notch by -secretase inhibitors, respectively. From this cadre of Notch-regulated genes, we developed candidate transcriptomic signatures that were trained on a breast cancer patient dataset (the TCGA-BRCA cohort) and an optimal 20-gene signature was selected from analysis of the transcriptomes of a broader breast cancer cell line cohort. We validated the signature on two independent patient datasets (METABRIC and Oslo2) and it showed an improved coherence score and tumour specificity compared with previously published signatures. Furthermore, the signature score was particularly high for basal-like breast cancer, indicating an enhanced level of Notch signalling in this subtype. The signature score was increased after neoadjuvant treatment in the PROMIX and BEAUTY patient cohorts, and a lower signature score generally correlated with better clinical outcome. Collectively, the 20-gene transcriptional signature has the potential to better stratify patients and to evaluate the response of future Notch-based therapies for breast cancer.
2024-01-05 | GSE236749 | GEO
Project description:Dysregulated Notch signalling contributes to breast cancer development and progression, but validated tools to measure the level of Notch signalling in breast cancer subtypes and in response to systemic therapy are largely lacking. A transcriptomic signature of Notch signalling would thus be warranted, and in this report, we have established such a classifier. To generate the signature, we first identified Notch-regulated genes from six basal-like breast cancer cell lines subjected to elevated and reduced Notch signalling by culturing on immobilized Notch ligand Jagged1 or blockade of Notch by -secretase inhibitors, respectively. From this cadre of Notch-regulated genes, we developed candidate transcriptomic signatures that were trained on a breast cancer patient dataset (the TCGA-BRCA cohort) and an optimal 20-gene signature was selected from analysis of the transcriptomes of a broader breast cancer cell line cohort. We validated the signature on two independent patient datasets (METABRIC and Oslo2) and it showed an improved coherence score and tumour specificity compared with previously published signatures. Furthermore, the signature score was particularly high for basal-like breast cancer, indicating an enhanced level of Notch signalling in this subtype. The signature score was increased after neoadjuvant treatment in the PROMIX and BEAUTY patient cohorts, and a lower signature score generally correlated with better clinical outcome. Collectively, the 20-gene transcriptional signature has the potential to better stratify patients and to evaluate the response of future Notch-based therapies for breast cancer.
2024-01-05 | GSE235052 | GEO
Project description:Epithelial-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is considered a key process driving tumor cell invasiveness and metastasis. Using breast cancer cell lines as a model system, we sought to discover gene-expression signatures of EMT with clinical and mechanistic relevance. A supervised comparison of epithelial and mesenchymal breast cancer lines defined a 200-gene EMT signature that was prognostic across multiple breast cancer cohorts. Immunostaining of LYN, a top-ranked EMT signature gene and Src-family tyrosine kinase, was associated with significantly shorter overall survival (P=0.02), and correlated with the basal-like (“triple-negative”) phenotype. In mesenchymal breast cancer lines, RNAi-mediated knockdown of LYN inhibited cell migration and invasion, but not proliferation. Dasatinib, a dual-specificity tyrosine kinase inhibitor, also blocked invasion (but not proliferation) at nanomolar concentrations that inhibit LYN kinase activity, suggesting that LYN is a likely target and invasion a relevant endpoint for dasatinib therapy. Our findings define a prognostically-relevant EMT signature in breast cancer, and identify LYN as a mediator of invasion and possible new therapeutic target (and theranostic marker for dasatinib response), with particular relevance to clinically-aggressive basal-like breast cancer. Cell Line: cell line(epithelial-like/fibroblast-like/normal breast fibroblasts) Keywords: Logical Set Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. HEEBO oligonucleotide microarrays from the Stanford Functional Genomics Facility were used to perform gene expression profiling of 20 human breast cell lines, in comparison to a universal RNA reference. Expression data were analyzed by Significance Analysis of Microarrays to identify a 200-gene signature characteristic of EMT.
2010-04-11 | E-GEOD-13915 | biostudies-arrayexpress
Project description:Gene Expression Signature of Microcalcification among Taiwanese Breast Cancer
| PRJNA610873 | ENA
Project description:Tumour hypoxia is a recognised driver of breast cancer pathology. The main cellular response to hypoxia is mediated by the hypoxia-inducible factors HIF1 and HIF2, and is controlled through the regulation of oxygen-labile HIFα subunits. HIF1α has a well-established role in breast cancer where it has also been shown to be regulated by growth factor signalling. However, the role of HIF2α has been less thoroughly researched. Here, the role of HIF2α was investigated in breast cancer cell lines and publicly available gene expression datasets to determine its relationship with HER2 receptor expression in breast cancer. Using an isogenic cell line model for HER2 overexpression, we establish a direct role for HER2 in driving HIF2α expression in breast cancer. The effect of HER2-mediated HIF2α expression on the cellular response to acute and chronic hypoxia was investigated in 2D and 3D cell line models, and through protein and gene expression analysis, HER2 was shown to drive an exacerbated hypoxic response in these cells. In growth assays, HER2-overexpressing cell lines were shown to be highly sensitive to HIF2-specific inhibition through HIF2α-targeted siRNA and treatment with the HIF2α-specific translation inhibitor C76. Additionally, survival analysis in a large, publicly available dataset demonstrated a relationship between HIF2α and poor disease-specific survival in HER2-overexpressing tumours. We demonstrate a novel role for HIF2α in driving an increased hypoxic response in breast cancer cells and suggest HIF2 signalling may be an important, targetable pathway in HER2-positive breast cancers.
2018-03-01 | GSE111246 | GEO