Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DNA methylation profile of triple negative breast cancer specific genes (validation)

ABSTRACT: Purpose Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression in tumour samples compared to normal samples. This study aimed to identify whether DNA methylation contributed to these gene expression changes in the same breast cancer cohort. Additionally, we aimed to identify a whole genome methylation profile that contributes to the progression from primary breast tumour to lymph node metastasis. Methods We used the DNA of 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues to perform 450K Illumina methylation arrays. The results were validated in an independent cohort of 70 primary TNBC samples. Results The gene expression of 16/38 TNBC-specific genes was associated with significantly altered methylation. Furthermore, altered methylation of 18 genes associated with lymph node metastasis was identified and validated in an independent cohort. Additionally, novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Conclusion This study has shown that DNA methylation plays an important role in altered gene expression patterns of TNBC-specific genes and is the first study to perform whole genome DNA methylation analysis that includes matched lymph node metastases in this breast cancer subtype. This novel insight into the progression of TNBC to secondary cancers may provide potential prognostic indicators for this hard-to-treat breast cancer subtype. Validation cohort (70 IDC TNBC samples)

ORGANISM(S): Homo sapiens

PROVIDER: GSE78754 | GEO | 2017/02/10

SECONDARY ACCESSION(S): PRJNA313440

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

DNA methylation profile of triple negative breast cancer specific genes (study)

Project description:Purpose Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression in tumour samples compared to normal samples. This study aimed to identify whether DNA methylation contributed to these gene expression changes in the same breast cancer cohort. Additionally, we aimed to identify a whole genome methylation profile that contributes to the progression from primary breast tumour to lymph node metastasis. Methods We used the DNA of 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues to perform 450K Illumina methylation arrays. The results were validated in an independent cohort of 70 primary TNBC samples. Results The gene expression of 16/38 TNBC-specific genes was associated with significantly altered methylation. Furthermore, altered methylation of 18 genes associated with lymph node metastasis was identified and validated in an independent cohort. Additionally, novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Conclusion This study has shown that DNA methylation plays an important role in altered gene expression patterns of TNBC-specific genes and is the first study to perform whole genome DNA methylation analysis that includes matched lymph node metastases in this breast cancer subtype. This novel insight into the progression of TNBC to secondary cancers may provide potential prognostic indicators for this hard-to-treat breast cancer subtype. study cohort

2017-02-10 | GSE78751 | GEO

Decreased expression of key tumour suppressor microRNAs is associated with lymph node metastases in triple negative breast cancer

Project description:Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-associated death rates. Triple negative breast cancers (TNBC) represent an important subtype that have an aggressive clinical phenotype, are associated with a higher likelihood of metastasis and are not responsive to current targeted therapies. miRNAs have emerged as an attractive candidate for molecular biomarkers and treatment targets in breast cancer, but their role in the progression of TNBC remains largely unexplored. This study has investigated miRNA expression profiles in 31 primary TNBC cases and in 13 lymph node metastases compared with 23 matched normal breast tissues to determine miRNAs associated with the initiation of this disease subtype and those associated with its metastasis. 71 miRNAs were differentially expressed in TNBC, the majority of which have previously been associated with breast cancer, including members of the miR-200 family and the miR-17-92 oncogenic cluster, suggesting that miRNAs involved in the initiation of TNBC are not subtype specific. However, the repertoire of miRNAs expressed in lymph node negative and lymph node positive TNBCs were largely distinct from one another. In particular, miRNA profiles associated with lymph node negative disease tended to be up-regulated, while those associated with lymph node positive disease were down-regulated and largely overlapped with the profiles of their matched lymph node metastases. miRNA expression profiles were examined in 31 primary TNBC cases and in 13 lymph node metastases compared with 23 matched normal breast tissues

2014-11-24 | E-GEOD-38167 | biostudies-arrayexpress

Decreased expression of key tumour suppressor microRNAs is associated with lymph node metastases in triple negative breast cancer

2014-11-24 | GSE38167 | GEO

Breast cancer tumors

Project description:The project analyzed 88 breast cancer clinical samples, including lymph node negative and positive primary tumors, lymph node metastases, and healthy tissue as control. All samples were combined with a super-SILAC mix that served as an internal standard for quantification.

2016-06-16 | MSV000079830 | MassIVE

Breast cancer tumors - System-wide Clinical Proteomics of Breast Cancer Reveals Global Remodeling of Tissue Homeostasis

2016-01-25 | PXD000815 | Pride

Downregulation of antigen presentation-associated pathway proteins in poor outcome triple-negative breast cancer patient tumors

Project description:Triple-negative breast cancer (TNBC) is a heterogeneous subtype with varying disease outcomes. Tumor infiltrating lymphocytes (TILs) are frequent in TNBC and have been shown to correlate with outcome, suggesting an immunogenic component in this subtype. However, other factors, intrinsic to the cancer cells, may also influence outcome. To identify proteins and molecular pathways associated with recurrence in TNBC, 34 formalin-fixed paraffin-embedded (FFPE) primary TNBC tumors were investigated by global proteomic profiling using TMT-HILIC-LC-MS/MS. Approximately half of the patients were lymph node-negative and remained free of local or distant metastasis within 10 years follow-up, while the other half developed distant metastasis. Proteomic profiling identified >4000 proteins, of which 63 exhibited altered expression in primary tumors of recurrence versus recurrence-free patients. Importantly, down-regulation of proteins in the major histocompatibility complex (MHC) class I antigen presentation pathways were enriched, including TAP1, TAP2, CALR, HLA-A, ERAP1 and TAPBP, and were associated with significantly shorter recurrence-free and overall survival. In addition, proteins involved in cancer cell proliferation and growth, including GBP1, RAD23B, WARS and STAT1, also exhibited altered expression in primary tumors of recurrence versus recurrence-free patients. The association between the antigen-presentation pathway and outcome were validated in a second sample set of 10 primary TNBC tumors and corresponding metastases using proteomics and in a large public gene expression database of 249 TNBC and 580 basal-like breast cancer cases. Our study demonstrates that down-regulation of antigen presentation is a key mechanism for TNBC cells to avoid immune surveillance, allowing continued growth and spread.

2018-10-26 | PXD005544 | Pride

Transcriptomic survey of lymph node-positive vs. - negative ductal breast cancer

Project description:Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes. The transcriptomic study comprises 16 samples from Lymph node metastasis from infiltrating ductal breast carcinoma, 18 samples from Primary node-positive infiltrating ductal,7 samples from Primary node-negative infiltrating ductal and 3 samples from Unaffected lymph node were included. Their RNA was isolated and prepared for hybridization to human Affymetrix GeneChip arrays.

2013-03-05 | E-GEOD-44408 | biostudies-arrayexpress

Prognostic value of biomarkers EpCAM and B-crystallin is associated with lymphatic metastasis in breast cancer by iTRAQ analysis

Project description:Metastasis is responsible for the majority of deaths in a variety of cancer types, including breast cancer. Although several factors or biomarkers have been identified to predict the outcome of patients with breast cancer, few studies have been conducted to identify metastasis-associated biomarkers. Quantitative iTRAQ proteomics analysis was used to detect differentially expressed proteins between lymph node metastases and their paired primary tumor tissues from 23 patients with metastatic breast cancer. Immunohistochemistry was performed to validate the expression of two upregulated (EpCAM, FADD) and two downregulated (NDRG1, αB-crystallin) proteins in 190 paraffin-embedded tissue samples. These four proteins were further analyzed for their correlation with clinicopathological features in 190 breast cancer patients. We identified 637 differentially regulated proteins (397 upregulated and 240 downregulated) in lymph node metastases compared with their paired primary tumor tissues. Furthermore, bioinformatics analysis using GEO profiling confirmed the difference in the expression of EpCAM between metastases and primary tumors tissues. Two upregulated (EpCAM, FADD) and two downregulated (NDRG1, αB-crystallin) proteins were associated with the progression of breast cancer. Obviously, EpCAM plays a role in the metastasis of breast cancer cells to the lymph node. We further identified αB-crystallin as an independent biomarker to predict lymph node metastasis and the outcome of breast cancer patients.

2019-08-29 | PXD013931 | Pride

Single cell RNA sequencing of primary breast cancer.

Project description:We performed single cell RNA sequencing (RNA-seq) for 549 primary breast cancer cells and lymph node metastases from 11 patients with distinct molecular subtypes (BC01-BC02, estrogen receptor positive (ER+); BC03, double positive (ER+ and HER2+); BC03LN, lymph node metastasis of BC03; BC04-BC06, human epidermal growth factor receptor 2 positive (HER2+); BC07-BC11, triple-negative breast cancer (TNBC); BC07LN, lymph node metastasis of BC07) and matched bulk tumors. We separated these single cells into epithelial tumor and tumor-infiltrating immune cells using inferred CNVs from RNA-seq. The refined single cell profiles for the tumor and immune cells provide key expression signatures of breast cancer and the surrounding microenvironment.

2016-12-09 | GSE75688 | GEO

Transcriptomic survey of lymph node-positive vs. - negative ductal breast cancer

Project description: Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and –positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes.

2013-03-05 | GSE44408 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data