Gene Expression Profiles in Breast Cancer to Identify Estrogen Receptor Target Genes

2008 ◽  
Vol 8 (5) ◽  
pp. 448-454 ◽  
Author(s):  
M. Nagai ◽  
M. Brentani
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals Impact of 70-Gene Signature Use on Adjuvant Chemotherapy Decisions in Patients With Estrogen Receptor–Positive Early Breast Cancer: Results of a Prospective Cohort Study

2017 ◽  
Vol 35 (24) ◽  
pp. 2814-2819 ◽  
Author(s):  
Anne Kuijer ◽  
Marieke Straver ◽  
Bianca den Dekker ◽  
Annelotte C.M. van Bommel ◽  
Sjoerd G. Elias ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Early Stage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Signature ◽  
Early Stage Breast Cancer ◽  
Er Positive ◽  
Test Result

Purpose Gene-expression profiles increasingly are used in addition to conventional prognostic factors to guide adjuvant chemotherapy (CT) decisions. The Dutch guideline suggests use of validated gene-expression profiles in patients with estrogen receptor (ER) –positive, early-stage breast cancer without overt lymph node metastases. We aimed to assess the impact of a 70-gene signature (70-GS) test on CT decisions in patients with ER-positive, early-stage breast cancer. Patients and Methods In a prospective, observational, multicenter study in patients younger than 70 years old who had undergone surgery for ER-positive, early-stage breast cancer, physicians were asked whether they intended to administer adjuvant CT before deployment of the 70-GS test and after the test result was available. Results Between October 1, 2013, and December 31, 2015, 660 patients, treated in 33 hospitals, were enrolled. Fifty-one percent of patients had pT1cN0, BRII, HER2-Neu-negative breast cancer. On the basis of conventional clinicopathological characteristics, physicians recommended CT in 270 (41%) of the 660 patients and recommended withholding CT in 107 (16%) of the 660 patients. For the remaining 43% of patients, the physicians were unsure and unable to give advice before 70-GS testing. In patients for whom CT was initially recommended or not recommended, 56% and 59%, respectively, were assigned to a low-risk profile by the 70-GS (κ, 0.02; 95% CI, -0.08 to 0.11). After disclosure of the 70-GS test result, the preliminary advice was changed in 51% of patients who received a recommendation before testing; the definitive CT recommendation of the physician was in line with the 70-GS result in 96% of patients. Conclusion In this prospective, multicenter study in a selection of patients with ER-positive, early-stage breast cancer, 70-GS use changed the physician-intended recommendation to administer CT in half of the patients.

scholarly journals Comparison and Identification of Estrogen-Receptor Related Gene Expression Profiles in Breast Cancer of Different Ethnic Origins

2008 ◽  
Vol 1 ◽  
pp. BCBCR.S626 ◽  
Author(s):  
Hsiao-Wei Chen ◽  
Hsuan-Cheng Huang ◽  
Yi-Shing Lin ◽  
King-Jen Chang ◽  
Wen-Hung Kuo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Microarray Experiment ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Increased Risk ◽  
Ethnic Origins

The interactions between genetic variants in estrogen receptor (ER) have been identified to be associated with an increased risk of breast cancer. Available evidence indicates that genetic variance within a population plays a crucial role in the occurrence of breast cancer. Thus, the comparison and identification of ER-related gene expression profiles in breast cancer of different ethnic origins could be useful for the development of genetic variant cancer therapy. In this study, we performed microarray experiment to measure the gene expression profiles of 59 Taiwanese breast cancer patients; and through comparative bioinformatics analysis against published U.K. datasets, we revealed estrogen-receptor (ER) related gene expression between Taiwanese and British patients. In addition, SNP databases and statistical analysis were used to elucidate the SNPs associated with ER status. Our microarray results indicate that the expression pattern of the 65 genes in ER+ patients was dissimilar from that of the ER- patients. Seventeen mutually exclusive genes in ER-related breast cancer of the two populations with more than one statistically significant SNP in genotype and allele frequency were identified. These 17 genes and their related SNPs may be important in population-specific ER regulation of breast cancer. This study provides a global and feasible approach to study population-unique SNPs in breast cancer of different ethnic origins.

scholarly journals Identification and characterization of critical genes associated with tamoxifen resistance in breast cancer

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10468
Author(s):  
Kai Zhang ◽  
Kuikui Jiang ◽  
Ruoxi Hong ◽  
Fei Xu ◽  
Wen Xia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Target Genes ◽  
Expression Profiles ◽  
Tamoxifen Resistance ◽  
Gene Expression Profiles ◽  
Gene Expression Omnibus ◽  
Ppi Network ◽  
Hub Genes ◽  
Mcf 7

Background Tamoxifen resistance in breast cancer is an unsolved problem in clinical practice. The aim of this study was to determine the potential mechanisms of tamoxifen resistance through bioinformatics analysis. Methods Gene expression profiles of tamoxifen-resistant MCF-7/TR and MCF-7 cells were acquired from the Gene Expression Omnibus dataset GSE26459, and differentially expressed genes (DEGs) were detected with R software. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. A protein–protein interaction (PPI) network was generated, and we analyzed hub genes in the network with the Search Tool for the Retrieval of Interacting Genes database. Finally, we used siRNAs to silence the target genes and conducted the MTS assay. Results We identified 865 DEGs, 399 of which were upregulated. GO analysis indicated that most genes are related to telomere organization, extracellular exosomes, and binding-related items for protein heterodimerization. PPI network construction revealed that the top 10 hub genes—ACLY, HSPD1, PFAS, GART, TXN, HSPH1, HSPE1, IRAS, TRAP1, and ATIC—might be associated with tamoxifen resistance. Consistently, RT-qPCR analysis indicated that the expression of these 10 genes was increased in MCF-7/TR cells comparing with MCF-7 cells. Four hub genes (TXN, HSPD1, HSPH1 and ATIC) were related to overall survival in patients who accepted tamoxifen. In addition, knockdown of HSPH1 by siRNA may lead to reduced growth of MCF-7/TR cell with a trend close to significance (P = 0.07), indicating that upregulation of HSPH1 may play a role in tamoxifen resistance. Conclusion This study revealed a number of critical hub genes that might serve as therapeutic targets in breast cancer resistant to tamoxifen and provided potential directions for uncovering the mechanisms of tamoxifen resistance.

scholarly journals Integrative Analysis with Monte Carlo Cross-Validation Reveals miRNAs Regulating Pathways Cross-Talk in Aggressive Breast Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Antonio Colaprico ◽  
Claudia Cava ◽  
Gloria Bertoli ◽  
Gianluca Bontempi ◽  
Isabella Castiglioni
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cross Talk ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Integrated Approach ◽  
Random Forest Classification ◽  
Forest Classification ◽  
Stem Cell Pluripotency

In this work an integrated approach was used to identify functional miRNAs regulating gene pathway cross-talk in breast cancer (BC). We first integrated gene expression profiles and biological pathway information to explore the underlying associations between genes differently expressed among normal and BC samples and pathways enriched from these genes. For each pair of pathways, a score was derived from the distribution of gene expression levels by quantifying their pathway cross-talk. Random forest classification allowed the identification of pairs of pathways with high cross-talk. We assessed miRNAs regulating the identified gene pathways by a mutual information analysis. A Fisher test was applied to demonstrate their significance in the regulated pathways. Our results suggest interesting networks of pathways that could be key regulatory of target genes in BC, including stem cell pluripotency, coagulation, and hypoxia pathways and miRNAs that control these networks could be potential biomarkers for diagnostic, prognostic, and therapeutic development in BC. This work shows that standard methods of predicting normal and tumor classes such as differentially expressed miRNAs or transcription factors could lose intrinsic features; instead our approach revealed the responsible molecules of the disease.

scholarly journals Distinct gene expression profiles between primary breast cancers and brain metastases from pair-matched samples

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Takayuki Iwamoto ◽  
Naoki Niikura ◽  
Rin Ogiya ◽  
Hiroyuki Yasojima ◽  
Ken-ichi Watanabe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Brain Metastases ◽  
Therapeutic Target ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Breast Cancers ◽  
Mesenchymal Transition ◽  
Matched Samples

Abstract Our objectives were to determine whether clinic-pathological markers and immune-related gene signatures in breast cancer exhibit any change upon brain metastasis and whether previously reported genes significantly associated with brain metastases and the epithelial-mesenchymal transition (EMT) were reproducible and consistent in our dataset. Sixteen pair-matched samples from primary breast cancers and brain metastases diagnosed were collected from the Japan Clinical Oncology Group Breast Cancer Study Group. Gene expression profiles for immune-, brain metastases-, and EMT-related genes were compared between primary breast cancers and brain metastases. Potential therapeutic target genes of 41 FDA-approved or under-investigation agents for brain metastases were explored. Immune-related signatures exhibited significantly lower gene expression in brain metastases than in primary breast cancers. No significant differences were detected for the majority of genes associated with brain metastases and EMT in the two groups. Among 41 therapeutic target candidates, VEGFA and DNMT3A demonstrated significantly higher gene expression in brain metastases. We found that distinct patterns of gene expression exist between primary breast cancers and brain metastases. Further studies are needed to explore whether these distinct expression profiles derive from or underlie disease status and compare these features between metastases to the brain and other sites.

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