Spatial Profiling Identifies Prognostic Features of Response to Adjuvant Therapy in Triple Negative Breast Cancer (TNBC)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA906492 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Nanostring DSP was performed on 25 TMA cores from TNBC patients with separate tumour and stroma compartment samples De proteins were identified in tumour and stromal compartments
2022-11-29 | GSE218973 | GEO
Project description:The lack of prognostic biomarkers and therapeutic targets in triple-negative breast cancer (TNBC) underscores an urgent need for the identification of novel biomarkers and effective treatment targets. In this study, we collected tumor and adjacent normal samples of four TNBC and four non-TNBC patients for RNA sequencing.TNBC exhibited distinguished gene expression and splicing patterns in contrast to non-TNBC. Notably, we identified four genes that were exclusively responsive and significantly correlated with prognosis in TNBC, but not non-TNBC. Immunohistochemical analysis confirmed the preferential expression of Chloride Intracellular Channel 3 (CLIC3) in TNBC, proposing CLIC3 as a potential prognostic biomarker for TNBC.
2025-10-07 | GSE267442 | GEO
Project description:The lack of prognostic biomarkers and therapeutic targets in triple-negative breast cancer (TNBC) underscores an urgent need for the identification of novel biomarkers and effective treatment targets. In this study, we collected tumor and adjacent normal samples of four TNBC and four non-TNBC patients for whole-exome sequencing (WES).Comparative WES analysis uncovered the distinct landscape of somatic mutations and driver genes in TNBC.
2025-10-07 | GSE267443 | GEO
Project description:Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer due to lack of effective targeted therapies. Here, we report that the expression of miR-4417 is suppressed during the progression of TNBC cells from non-malignant to the malignant stage. miR-4417 is localized to chromosome 1p36, a region with high loss of heterozygosity in multiple cancers, and its biogenesis is DICER-dependent. Low expression of miR-4417 is significantly associated with worse prognosis in TNBC patients, while overexpression of miR-4417 is sufficient to inhibit migration and tumorigenecity of TNBC cells in vitro. Overall, our findings suggest that miR-4417 exerts a tumor suppressive effect and thereby could serve as a prognostic biomarker and therapeutic tool against TNBC. We used microarrays to profile the global miRNA changes during EMT to identify putative tumor suppressors and prognostic biomarkers for TNBC.
2019-10-15 | GSE121657 | GEO
Project description:Triple-negative breast cancer represents approximately 15–20% of all reported breast cancer cases, and is characterized by a shorter survival time and higher mortality rates compared to other breast cancer sub-types. Tumor microenvironment (TME) refers to the internal and external environment of tumor tissue. Increasing evidence indicates that a tumor’s microenvironment is tightly associated with the immunological surveillance and defense during the development of breast cancer. Although oncology studies employing digital dissection methodologies have provided some insight on the biological features of TME, the development of methods to investigate the cellular composition of the tumor microenvironment remain an important research priority. In this study, we extracted whole transcriptome from 30 Triple-negative breast cancer (TNBC) patients and then used bioinformatics approaches to characterize cell type content in tumor tissue compared with para-cancerous tissue. We identified 4 types of enriched immune cells and 6 types of downregulated immune cells in the tumor tissue samples. After comprehensive bioinformatics analyses, we developed an ‘immune infiltration score’ (IIS) to quantitatively model immune cell infiltration in TNBC. To demonstrate the utility of the IIS, we used 2 independent datasets for validation. We found that patients with a higher IIS showing a longer progression-free survival time and significantly better prognosis than those with a lower IIS value. In sum, we explored the immune infiltration landscape in 30 TNBC patients and provided a novel and reliable biomarker IIS to evaluate the progression-free survival and prognosis in the TNBC patients.
2021-10-18 | E-MTAB-10886 | biostudies-arrayexpress
Project description:There are no widely-accepted prognostic markers currently available to predict outcomes in patients with triple-negative breast cancer (TNBC), and no targeted therapies with confirmed benefit. We have used MALDI mass spectrometry imaging (MSI) of tryptic peptides to compare regions of cancer and benign tissue in 10 formalin-fixed, paraffin-embedded sections of TNBC tumors. Proteins were identified by reference to a peptide library constructed by LC-MALDI-MS/MS analyses of the same tissues. The prognostic significance of proteins that distinguished between cancer and benign regions was estimated by Kaplan-Meier analysis of their gene expression from public databases. Among peptides that distinguished between cancer and benign tissue in at least 3 tissues with a ROC area under the curve >0.7, 14 represented proteins identified from the reference library, including proteins not previously associated with breast cancer. Initial network analysis using the STRING database showed no obvious functional relationships except among collagen subunits COL1A1, COL1A2, and COL63A, but manual curation, including the addition of EGFR to the analysis, revealed a unique network connecting 10 of the 14 proteins. Kaplan-Meier survival analysis to examine the relationship between tumor expression of genes encoding the 14 proteins, and recurrence-free survival (RFS) in patients with basal-like TNBC showed that, compared to low expression, high expression of nine of the genes was associated with significantly worse RFS, most with hazard ratios >2. In contrast, in estrogen receptor-positive tumors, high expression of these genes showed only low, or no, association with worse RFS. These proteins are proposed as putative markers of RFS in TNBC, and some may also be considered as possible targets for future therapies.
2019-05-06 | PXD013397 | Pride
Project description:Recent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets. We identified and confirmed four distinct, stable TNBC subtypes: (1) Luminal-AR (LAR); 2) Mesenchymal (MES); 3) Basal-Like Immune-Suppressed (BLIS), and 4) Basal-Like Immune-Activated (BLIA). RNA profiling analysis was conducted on 198 TNBC tumors (ER-negativity defined as Allred Scale value â¤2) with >50% cellularity (discovery set: n=84; validation set: n=114)
2015-12-18 | E-GEOD-76124 | biostudies-arrayexpress
Project description:Triple negative breast cancer is an aggressive type of breast cancer with very little treatment options. TNBC is very heterogeneous with large alterations in the genomic, transcriptomic, and proteomic landscapes leading to various subtypes with differing responses to therapeutic treatments. We applied a multi-omics data integration method to evaluate the correlation of important regulatory features in TNBC BRCA1 wild-type MDA-MB-231 and TNBC BRCA1 5382insC mutated HCC1937 cells compared with normal epithelial breast MCF10A cells. The data includes DNA methylation, RNAseq, protein, phosphoproteomics, and histone post-translational modification. Data integration methods identified regulatory features from each omics method had greater than 80% positive correlation within each TNBC subtype. Key regulatory features at each omics level were identified distinguishing the three cell lines and were involved in important cancer related pathways such as TGFbeta signaling, PI3K/AKT/mTOR, and Wnt/beta-catenin signaling.
2021-06-24 | PXD025238 | Pride
Project description:The EN1 transcription factor drives neural features and brain metastases in triple negative breats cancer (TNBC)
| PRJNA495138 | ENA
Project description:Purpose: The purpose of this study was to independently validate two biomarkers, a 44-gene DNA Damage Immune Response (DDIR) signature and stromal tumor-infiltrating lymphocytes (sTILs), as prognostic markers in TNBC patients treated with adjuvant doxorubicin (A) and cyclophosphamide (C) in SWOG 9313. Materials & Methods: 425 centrally determined TNBC cases from S9313 were identified. DDIR signature was performed on RNA isolated from FFPE tumor tissue (n=381), and samples were classified as DDIR-negative or positive using predefined cutoffs. Evaluation of sTILs was performed as previously described. Markers were tested for prognostic value for disease-free and overall survival (DFS, OS) using Cox regression models adjusted for treatment assignment nodal status and tumor size. Results: Among 425 TNBC patients, median age was 45 years, and 33% were node-positive. DDIR was successfully tested in 90% (381/425) of cases, of which 62% were DDIR signature-positive. DDIR signature positivity was associated with improved DFS (HR=0.67; 95% CI 0.48–0.92, P=0.014) and OS (HR=0.61; 95% CI 0.43–0.89, P=0.009). sTILs density assessment was available in 99% of patients and was associated with improved DFS (HR=0.70; 95% CI 0.51–0.96, P=0.028 for sTILs density ≥20% vs. <20%) and OS (HR=0.59; 95% CI 0.41–0.85, P=0.004 for sTILs density ≥20% vs. <20%). The DDIR signature score and sTILs density were moderately correlated (r=0.62) which precluded statistical significance for DFS in a joint model (P=0.08 for DDIR and P=0.25 for sTILs). Conclusion: The prognostic role of sTILs and DDIR in early-stage TNBC was confirmed. DDIR signature conferred improved prognosis in two-thirds of TNBC patients treated with adjuvant AC. DDIR signature has potential to stratify outcome and identify patients with less projected benefit following AC chemotherapy. Clinical trial number: Int0137 (The trial pre-dates Clinicaltrial.Gov website establishment)
2019-09-13 | GSE137356 | GEO