Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA248722 | ENA |
REPOSITORIES: ENA
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Project description:Triple negative breast cancers (TNBCs) comprise a heterogeneous group of cancers with varying prognoses, presenting a challenge for effective clinical management. Epigenetic alterations in the cancer methylome are common in breast cancer and provide novel options for tumor stratification on the basis of prognosis. Advances in genome-wide DNA methylation technology have enabled more comprehensive identification of potential epigenetic diagnostic and prognostic cancer biomarkers. Here, we use MBDCap-Seq to perform genome-wide DNA methylation profiling from archival TNBC and matched normal DNA samples. We identified 822 differentially methylated regions (DMRs) comprising 308 genes affected by cancer-specific promoter hypermethylation. Notably, 51 of these genes are also recurrently mutated in breast cancer, seven of which include members of the axon guidance pathway recently implicated in tumor initiation and progression. Using TCGA methylation data as an independent validation cohort for TNBCs (n= 73), we showed that 36 genomic regions were specific for TNBCs, including both promoter and gene body hypermethyled loci. Importantly, we stratified TNBCs into three distinct methylation clusters associated with better or worse prognosis. Furthermore, we identified a “survival” methylation signature consisting of 17 DMRs that show strong regional association with overall survival, 16 of which overlap DNase1 hypersensitive sites. Notably three of these “survival” DMRs are located in the bi-directional promoter and gene bodies of WT1 gene and its anti-sense counter-part WT1-AS. Together, our data identifies for the first time a cancer DNA methylation diagnostic and prognostic signature that promises to stratify TNBCs for more personalized management.
2014-12-31 | GSE58020 | GEO
Project description:Development of an immune-related prognostic biomarker for triple-negative breast cancer
| PRJEB47208 | ENA
Project description:Triple negative breast cancer (TNBC) accounts for 15-20% of all breast carcinomas and it is clinically characterized by an aggressive phenotype and bad prognosis. TNBC does not benefit from any targeted therapy, so further characterization is needed to define subgroups with potential therapeutic value. In this work, the proteomes of one hundred twenty-five formalin-fixed paraffin-embedded samples from patients diagnosed with triple negative breast cancer were analyzed by mass spectrometry using data-independent acquisition. Hierarchical clustering, probabilistic graphical models and Significance Analysis of Microarrays were used to characterize molecular groups. Additionally, a predictive signature related with relapse was defined. Two molecular groups with differences in several biological processes as glycolysis, translation and immune response, were defined in this cohort, and a prognostic signature based on the abundance of proteins RBM3 and NIPSNAP1 was defined. This predictor split the population into low-risk and high-risk groups. The differential processes identified between the two molecular groups may serve to design new therapeutic strategies in the future and the prognostic signature could be useful to identify a population at high-risk of relapse that could be directed to clinical trials.
2022-02-14 | PXD021491 | Pride
Project description:Epigenetic deregulation is a critical event in human malignancies. A number of DNA methylation markers are currently under evaluation as diagnostic and prognostic biomarkers for many cancers. However, its potential role in hepatocellular carcinoma (HCC) is under-explored. Aims: To develop a DNA methylation-based prognostic signature in surgically resected HCC Tumors from 224 HCC resected patients, 10 normal Liver individuals and 9 Cirrhotic patients were analyzed. Methylome profiling was done with Illumina HumanMethylation450 (485,000 CpG, 96% of known CpG islands). We selected probes in CpG islands located in promoters, hypermethylated (B value higher than 50%) in at least 5% of the tumors and hypomethylated (B value lower than 33%) in more than 90% of normal liver.
2015-02-13 | E-GEOD-56588 | biostudies-arrayexpress
Project description:Methylome analysis of different histological thyroid lesions and clinical features, aiming to better understand the DNA methylation deregulation of TC and to identify a prognostic epigenetic signature in well differentiated thyroid carcinomas.
2017-10-20 | GSE97466 | GEO
Project description:A microRNA signature identifies four subtypes of triple-negative breast cancer II
| PRJNA341352 | ENA
Project description:A microRNA signature identifies four subtypes of triple-negative breast cancer I
| PRJNA341348 | ENA
Project description:When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post NACT samples to predict relapse.
2022-09-20 | GSE185507 | 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:Breast cancer is genetically and clinically heterogeneous. Triple negative cancer (TNBC) is a subtype of breast cancer usually associated with poor outcome and lack of benefit from target therapy. A pathway analysis in a microarray study was performed using TNBC compared with non-triple negative breast cancer (non-TNBC). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 (FZD7), Low density lipoprotein receptor-related protein 6 (LRP6) and transcription factor 7 (TCF7) has been observed in TNBC. Focus was given to the Wnt pathway receptor, FZD7. To validate its function, inhibition of FZD7 using FZD7shRNA was carried out. Notably decreased cell proliferation, suppressed invasiveness and colony formation in triple negative MDA-MB-231 and BT-20 cells were observed. Mechanism study indicated that these effects occurred through silencing the canonical Wnt signaling pathway, as evidenced by loss of nuclear accumulation of ï?¢-catenin and decreased transcriptional activity of TCF7. In vivo study revealed that FZD7shRNA significantly suppressed the tumor formation in xenotransplation mice due to decrease cell proliferation. Our finding suggests that FZD7 involved canonical Wnt signaling pathway is essential for tumorigenesis of TNBC. Thus, FZD7 may be a biomarker and a potential therapeutic target for triple negative breast cancer. 14 pretreatment non-triple negative breast tumors compare with 5 triple negative breast tumor.
2011-06-01 | E-GEOD-27447 | biostudies-arrayexpress