Abstract 4698: Gene expression profiles of triple negative breast cancer epithelial and stromal cells are predictive of treatment response.

2013 ◽  
Author(s):  
Bojana Jovanovic ◽  
Steven X. Chen ◽  
Brian D. Lehmann ◽  
Kimberly N. Johnson ◽  
Violeta Sanchez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Treatment Response ◽  
Triple Negative Breast Cancer ◽  
Stromal Cells ◽  
Triple Negative ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals Analysis of gene expression patterns in triple negative breast cancer: MERTK and WHSC1L1.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Black Women ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Primary Tumors

Triple negative breast cancer (TNBC) shares overlap with the basal molecular subtype of breast cancer and is more frequently diagnosed in African-American (black) women for reasons not understood (1,2). To understand genes whose expression may be of pertinence to the development or progression of triple negative breast cancer, we mined published microarray data (3,4) comparing global gene expression profiles of TNBC histology groups, identifying genes whose expression changed the least between among TNBCs, suggesting that these genes may be important for TNBC biology. We identified the MER proto-oncogene tyrosine kinase MERTK and the Wolf-Hirschhorn syndrome candidate 1-like 1 WHSC1L1 among the genes whose expression differed the least when comparing TNBC cases and subtypes. In another dataset, MERTK and WHSCL1 were found to be differentially expressed in TNBC when comparing primary tumors of the breast to normal breast tissue. Kaplan-Meier survival analysis revealed that expression levels of MERTK and WHSCL1 correlated with survival outcomes in human breast cancer, and that this correlation differed based on race of the patient. MERTK and WHSCL1 may be of relevance in understanding the etiology or progression of triple negative breast cancer.

scholarly journals Gene Expression Profiles Induced by High-dose Ionizing Radiation in MDA-MB-231 Triple-negative Breast Cancer Cell Line

2019 ◽  
Vol 16 (4) ◽  
pp. 257-266 ◽  
Author(s):  
VALENTINA BRAVATÀ ◽  
FRANCESCO PAOLO CAMMARATA ◽  
LUIGI MINAFRA ◽  
ROSA MUSSO ◽  
GAIA PUCCI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Ionizing Radiation ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cell Line ◽  
Triple Negative ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cancer Cell Line ◽  
High Dose

Identification of CCNB2 expression in triple-negative breast cancer based on bioinformatics results

2021 ◽  
Author(s):  
jintao cao ◽  
SHUAI SUN ◽  
RAN LI ◽  
RUI MIN ◽  
XINGYU FAN ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Protein Complex ◽  
Triple Negative ◽  
Expression Profiles ◽  
Pathway Enrichment Analysis ◽  
Analysis Tool ◽  
The Core ◽  
Core Genes

Abstract Background The current epidemiology shows that the incidence of breast cancer is increasing year by year and tends to be younger. Triple-negative breast cancer is the most malignant of breast cancer subtypes. The application of bioinformatics in tumor research is becoming more and more extensive. This study provided research ideas and basis for exploring the potential targets of gene therapy for triple-negative breast cancer (TNBC). Methods We analyzed three gene expression profiles (GSE64790、GSE62931、GSE38959) selected from the Gene Expression Omnibus (GEO) database. The GEO2R online analysis tool was used to screen for differentially expressed genes (DEGs) between TNBC and normal tissues. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to identify the pathways and functional annotation of DEGs. Protein–protein interaction network of these DEGs were visualized by the Metascape gene-list analysis tool so that we could find the protein complex containing the core genes. Subsequently, we investigated the transcriptional data of the core genes in patients with breast cancer from the Oncomine database. Moreover, the online Kaplan–Meier plotter survival analysis tool was used to evaluate the prognostic value of core genes expression in TNBC patients. Finally, immunohistochemistry (IHC) was used to evaluated the expression level and subcellular localization of CCNB2 on TNBC tissues. Results A total of 66 DEGs were identified, including 33 up-regulated genes and 33 down-regulated genes. Among them, a potential protein complex containing five core genes was screened out. The high expression of these core genes was correlated to the poor prognosis of patients suffering breast cancer, especially the overexpression of CCNB2. CCNB2 protein positively expressed in the cytoplasm, and its expression in triple-negative breast cancer tissues was significantly higher than that in adjacent tissues. Conclusions CCNB2 may play a crucial role in the development of TNBC and has the potential as a prognostic biomarker of TNBC.

Epigenetic Reprogramming and Landscape of Transcriptomic Interactions: Impending Therapeutic Interference of Triple-Negative Breast Cancer in Molecular Medicine

2021 ◽  
Vol 21 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Treatment Decision ◽  
Copy Number Variations ◽  
Molecular Medicine ◽  
Breast Cancers ◽  
Breast Carcinogenesis

: The mechanisms governing the development and progression of cancers are believed to be the consequence of hereditary deformities and epigenetic modifications. Accordingly, epigenetics has become an incredible and progressively explored field of research to discover better prevention and therapy for neoplasia, especially triple-negative breast cancer (TNBC). It represents 15–20% of all invasive breast cancers and will, in general, have bellicose histological highlights and poor clinical outcomes. In the early phases of triple-negative breast carcinogenesis, epigenetic deregulation modifies chromatin structure and influences the plasticity of cells. It up-keeps the oncogenic reprogramming of malignant progenitor cells with the acquisition of unrestrained selfrenewal capacities. Genomic impulsiveness in TNBC prompts mutations, copy number variations, as well as genetic rearrangements, while epigenetic remodeling includes an amendment by DNA methylation, histone modification, and noncoding RNAs of gene expression profiles. It is currently evident that epigenetic mechanisms assume a significant part in the pathogenesis, maintenance, and therapeutic resistance of TNBC. Although TNBC is a heterogeneous malaise that is perplexing to describe and treat, the ongoing explosion of genetic and epigenetic research will help to expand these endeavors. Latest developments in transcriptome analysis have reformed our understanding of human diseases, including TNBC at the molecular medicine level. It is appealing to envision transcriptomic biomarkers to comprehend tumor behavior more readily regarding its cellular microenvironment. Understanding these essential biomarkers and molecular changes will propel our capability to treat TNBC adequately. This review will depict the different aspects of epigenetics and the landscape of transcriptomics in triple-negative breast carcinogenesis and their impending application for diagnosis, prognosis, and treatment decision with the view of molecular medicine.

scholarly journals Decoding Immune Heterogeneity of Triple Negative Breast Cancer and Its Association with Systemic Inflammation

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 911 ◽  
Author(s):  
Romero-Cordoba ◽  
Meneghini ◽  
Sant ◽  
Iorio ◽  
Sfondrini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Inflammation ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cytolytic Activity ◽  
Local Composition ◽  
Immune Infiltrate

Triple negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options. New opportunities are emerging from current comprehensive characterization of tumor immune infiltration and fitness. Therefore, effectiveness of current chemotherapies and novel immunotherapies are partially dictated by host inflammatory and immune profiles. However, further progress in breast cancer immuno-oncology is required to reach a detailed awareness of the immune infiltrate landscape and to determine additional reliable and easily detectable biomarkers. In this study, by analyzing gene expression profiles of 54 TNBC cases we identified three TNBC clusters displaying unique immune features. Deep molecular characterization of immune cells cytolytic-activity and tumor-inflammation status reveled variability in the local composition of the immune infiltrate in the TNBC clusters, reconciled by tumor-infiltrating lymphocytes counts. Platelet-to-lymphocyte ratio (PLR), a blood systemic parameter of inflammation evaluated using pre-surgical blood test data, resulted negatively correlated with local tumoral cytolytic activity and T cell–inflamed microenvironment, whereas tumor aggressiveness score signature positively correlated with PLR values. These data highlighted that systemic inflammation parameters may represent reliable and informative markers of the local immune tumor microenvironment in TNBC patients and could be exploited to decipher tumor infiltrate properties and consequently to select the most appropriate therapies.

scholarly journals Identification of Key Genes and Pathways in Triple-Negative Breast Cancer by Integrated Bioinformatics Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Pengzhi Dong ◽  
Bing Yu ◽  
Lanlan Pan ◽  
Xiaoxuan Tian ◽  
Fangfang Liu
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Prostate Gland ◽  
Neural Crest Cell ◽  
Nervous System Development ◽  
Chromosome 9 ◽  
Key Genes

Purpose. Triple-negative breast cancer refers to breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2). This study aimed to identify the key pathways and genes and find the potential initiation and progression mechanism of triple-negative breast cancer (TNBC). Methods. We downloaded the gene expression profiles of GSE76275 from Gene Expression Omnibus (GEO) datasets. This microarray Super-Series sets are composed of gene expression data from 265 samples which included 67 non-TNBC and 198 TNBC. Next, all the differentially expressed genes (DEGs) with p<0.01 and fold change ≥1.5 or ≤-1.5 were identified. Result. 56 upregulated and 151 downregulated genes were listed and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis was performed. These significantly changed genes were mainly involved in the biological process termed prostate gland morphogenesis, inner ear morphogenesis, cell maturation, digestive tract morphogenesis, autonomic nervous system development, monovalent inorganic anion homeostasis, neural crest cell development, regulation of dendrite extension and glial cell proliferation, immune system process termed T cell differentiation, regulation of immune response, and macrophage activation. Genes are mainly involved in the KEGG pathway termed Oocyte meiosis. All DEGs underwent survival analysis using datasets from The Cancer Genome Atlas (TCGA) integrated by cBioPortal, of which amplification of SRY-related HMG-box 8 (SOX8), androgen receptor (AR), and Chromosome 9 Open Reading Frame 152 (C9orf152) were significantly negative while Nik Related Kinase (NRK) and RAS oncogene family 30 (RAB30) were positively correlated to the life expectancy (p<0.05). Conclusions. In conclusion, these pathways and genes identified could help understanding the mechanism of development of TNBC. Besides, SOX8, AR, C9orf152, NRK and RAB30, and other key genes and pathways might be promising targets for the TNBC treatment.

scholarly journals TNBCtype: A Subtyping Tool for Triple-Negative Breast Cancer

2012 ◽  
Vol 11 ◽  
pp. CIN.S9983 ◽  
Author(s):  
Xi Chen ◽  
Jiang Li ◽  
William H. Gray ◽  
Brian D. Lehmann ◽  
Joshua A. Bauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Genomic Research ◽  
Data Matrix ◽  
Cancer Data ◽  
Subtyping Tool

Motivation Triple-negative breast cancer (TNBC) is a heterogeneous breast cancer group, and identification of molecular subtypes is essential for understanding the biological characteristics and clinical behaviors of TNBC as well as for developing personalized treatments. Based on 3,247 gene expression profiles from 21 breast cancer data sets, we discovered six TNBC subtypes from 587 TNBC samples with unique gene expression patterns and ontologies. Cell line models representing each of the TNBC subtypes also displayed different sensitivities to targeted therapeutic agents. Classification of TNBC into subtypes will advance further genomic research and clinical applications. Result We developed a web-based subtyping tool TNBCtype for candidate TNBC samples using our gene expression meta data and classification methods. Given a gene expression data matrix, this tool will display for each candidate sample the predicted subtype, the corresponding correlation coefficient, and the permutation P-value. We offer a user-friendly web interface to predict the subtypes for new TNBC samples that may facilitate diagnostics, biomarker selection, drug discovery, and the more tailored treatment of breast cancer.

scholarly journals Identification of TENM4 as a Novel Cancer Stem Cell-Associated Molecule and Potential Target in Triple Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 894 ◽  
Author(s):  
Roberto Ruiu ◽  
Giuseppina Barutello ◽  
Maddalena Arigoni ◽  
Federica Riccardo ◽  
Laura Conti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Gene Expression Profiles ◽  
Normal Breast ◽  
Metastatic Progression ◽  
Cancer Subtypes ◽  
Associated Proteins

Triple-negative breast cancer (TNBC) is insensitive to endocrine and Her2-directed therapies, making the development of TNBC-targeted therapies an unmet medical need. Since patients with TNBC frequently show a quicker relapse and metastatic progression compared to other breast cancer subtypes, we hypothesized that cancer stem cells (CSC) could have a role in TNBC. To identify putative TNBC CSC-associated targets, we compared the gene expression profiles of CSC-enriched tumorspheres and their parental cells grown as monolayer. Among the up-regulated genes coding for cell membrane-associated proteins, we selected Teneurin 4 (TENM4), involved in cell differentiation and deregulated in tumors of different histotypes, as the object for this study. Meta-analysis of breast cancer datasets shows that TENM4 mRNA is up-regulated in invasive carcinoma specimens compared to normal breast and that high expression of TENM4 correlates with a shorter relapse-free survival in TNBC patients. TENM4 silencing in mammary cancer cells significantly impaired tumorsphere-forming ability, migratory capacity and Focal Adhesion Kinase (FAK) phosphorylation. Moreover, we found higher levels of TENM4 in plasma from tumor-bearing mice and TNBC patients compared to the healthy controls. Overall, our results indicate that TENM4 may act as a novel biomarker and target for the treatment of TNBC.

scholarly journals Exploration of Tumor Microenvironment-Related Biomarkers for the Prognosis of Triple Negative Breast Cancer

2021 ◽  
Author(s):  
Xiaorui Han ◽  
Zaiyi Liu ◽  
Changhong Liang
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Stromal Cells ◽  
Prognostic Model ◽  
Triple Negative ◽  
High Efficiency ◽  
Functional Enrichment

Abstract Background: Triple negative breast cancer (TNBC) is one of the most disastrous breast cancer subtypes world widely. The tumor microenvironment (TME), especially the infiltration of immune and stromal cells, are highly related to the occurrence, development and prognosis of breast cancer. Therefore, exploration of TME-related biomarkers is greatly important for improving overall survival rate of TNBC patients. Methods: The open-assess Cancer Genome Atlas (TCGA) database provides gene expression profile for a variety of malignant tumors allowing researchers to explore genes demonstrating TME in the prognosis prediction of TNBC. In our present study, ESTIMATE algorithm was used to calculate the immune and stromal scores in accordance with the characteristics of specific genes in immune and stromal cells, and divide them into high and low-score groups. Limma R package was then utilized to screen differentially expressed genes (DEGs). After that, functional enrichment analysis and protein-protein interaction (PPI) network were performed to explore the bio-information of the DEGs and their encoded proteins. Subsequently, the identified these genes were further verified in the Gene Expression Omnibus (GEO) datasets. Results: Eight genes, including ACAP1, DUSP1, LYZGZMA, SASH3, CCL5, CD74, and DPT, were explored to closely related to the TME of TNBC. A prognostic model containing these selected genes was established with a high efficiency in the prediction of the poor prognosis of TNBC patients.Conclusion: An eight-gene prognostic model was a considerably reliable approach for predicting the overall survival of TNBC patients, and could help clinicians selecting personalized treatments for their TNBC patients.

Sign in / Sign up

Export Citation Format

Share Document