Development of an immune-related prognostic biomarker for triple-negative breast cancer
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ABSTRACT:
PROVIDER: PRJEB47208 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR6565680_1.fastq.gz | Fastqsanger.gz | |||
| ERR6565680_2.fastq.gz | Fastqsanger.gz | |||
| ERR6565690_1.fastq.gz | Fastqsanger.gz | |||
| ERR6565690_2.fastq.gz | Fastqsanger.gz | |||
| ERR6565700_1.fastq.gz | Fastqsanger.gz |
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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:The aim of this study was evaluate the transcriptome changes in the comparison between triple negative tumors with increased SPARC expression and triple negative tumors with decreased SPARC expression according to Nagai et al., 2011 (Breast Cancer Res Treat (2011) 126:1–14) The results generated could be of particular interest to better define the prognostic impact of SPARC expression in triple negative breast tumors
2018-07-01 | GSE98931 | GEO
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: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
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:Discrepancies in the prognosis of triple negative breast cancer exist between Caucasian and Asian populations. Yet, the gene signature of triple negative breast cancer specifically for Asians has not become available. Therefore, the purpose of this study is to construct a prediction model for recurrence of triple negative breast cancer in Taiwanese patients. Whole genome expression profiling of breast cancers from 185 patients in Taiwan from 1995 to 2008 was performed, and the results were compared to the previously published literature to detect differences between Asian and Western patients. Pathway analysis and Cox proportional hazard models were applied to construct a prediction model for the recurrence of triple negative breast cancer. Most expression data of samples (181/185) were reanalyzed from previous studies already uploaded to GEO (see "reanalysis of" links below). Four additional gene expression profiling data of triple negative breast cancer sample were added to this study.
2012-02-02 | E-GEOD-33095 | biostudies-arrayexpress
Project description:Discrepancies in the prognosis of triple negative breast cancer exist between Caucasian and Asian populations. Yet, the gene signature of triple negative breast cancer specifically for Asians has not become available. Therefore, the purpose of this study is to construct a prediction model for recurrence of triple negative breast cancer in Taiwanese patients.
2012-02-02 | GSE33095 | GEO
Project description:Connective Tissue Growth Factor, a Potential Prognostic Marker of Triple Negative Breast Cancer treatment
| PRJNA820464 | ENA
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 beta-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.
2011-06-01 | GSE27447 | GEO
Project description:Triple therapy reduced metastasis in triple-negative breast cancer.
| PRJNA832953 | ENA