scholarly journals Prometastatic Molecular Profiles in Breast Tumors From Socially Isolated Women

2018 ◽  
Vol 2 (3) ◽  
Author(s):  
Julienne E Bower ◽  
Stephen L Shiao ◽  
Peggy Sullivan ◽  
Donald M Lamkin ◽  
Robert Atienza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Social Isolation ◽  
Cancer Progression ◽  
Standard Error ◽  
Lymphovascular Invasion ◽  
Breast Tumors ◽  
M2 Macrophage ◽  
Socially Isolated

Abstract Background Social isolation is associated with accelerated breast cancer progression and increased disease recurrence and mortality, but the underlying biological mechanisms remain poorly understood. In preclinical models, beta-adrenergic signaling from fight-or-flight stress responses can stimulate prometastatic processes in the tumor microenvironment including upregulation of M2 macrophages, epithelial–mesenchymal transition (EMT), and lymphovascular invasion. This study examines whether the same pathways are upregulated in breast tumors from socially isolated cancer patients. Methods EMT and M1/M2 macrophage gene expression programs were analyzed by genome-wide transcriptional profiling, and lymphatic and vascular density were assessed by immunohistochemistry in primary tumors from 56 early-stage breast cancer patients who were part of the UCLA RISE study. Social isolation was quantified by the Social Provisions Scale, and disease characteristics were assessed by medical record review. General linear models were used to quantify differential gene expression across risk factor groups. Linear regression models were used to examine associations between social isolation and lymphovascular invasion. Results Tumors from socially isolated patients showed upregulated expression of genes involved in EMT (average score difference = +0.080 log2 mRNA abundance ± 0.034 standard error) and M2 macrophage polarization (+0.033 ± 0.014) as well as increased density of lymphatic vessels (β= –.29) but no difference in blood vessel density. TELiS promoter–based bioinformatics analyses indicated activation of CREB family transcription factors that mediate the gene-regulatory effects of β-adrenergic signaling (log2 fold-difference in promoter binding site prevalence: mean ± standard error = +0.49 ± 0.19). Conclusions Primary breast tumors from socially isolated patients show multiple prometastatic molecular alterations, providing a plausible biological pathway through which poor social support may accelerate breast cancer progression and defining new targets for intervention.

Gene expression profiling of circulating tumor cells from breast cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10769-10769
Author(s):  
M. M. Magbanua ◽  
J. E. Lang ◽  
J. Scott ◽  
J. R. Crothers ◽  
S. Federman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Metastatic Breast ◽  
Breast Tumors ◽  
Breast Cancer Patients

10769 Background: Levels of circulating tumor cells (CTC) have prognostic and predictive significance in metastatic breast cancer. However, since CTCs are extremely rare, little is known about the actual phenotype of these cells. In order to characterize these cells, we performed cDNA microarray analyses of CTC isolated from peripheral blood (PB) of breast cancer patients. Methods: CTCs were directly isolated via immunomagnetic enrichment (IE) followed by fluorescence activated cell sorting (FACS). Total RNA was then subjected to two rounds of linear amplification and hybridized to cDNA microarrays (∼40,000 cDNAs). Validation studies used spiked BT474 cells. Clinical studies used PB (10–20 ml) from patients with metastatic breast cancer. Results: Rare spiked tumor cells (e.g., 320 cells in 10 mL PB) were efficiently recovered by IE/FACS (50% yield). Expression profiles of recovered cells, both by TaqMan of a 37 gene panel as well as by global gene expression analysis, matched that of BT474 cells in culture. In contrast, these profiles were clearly distinct from that of normal PB, ruling out significant contamination from blood elements. In clinical studies, IE/FACS isolated small numbers of CTCs (10–1000 cells). Expression profiles of CTCs were compared to that of normal blood, primary breast tumors, and normal epithelial samples. Unsupervised hierarchical clustering revealed that CTC profiles were readily distinguished from that of normal blood and normal epithelium; and further analysis revealed that CTC cluster with a subset of primary breast tumors, particularly the basal-like phenotype. Candidate genes associated with the CTC phenotype were also identified. Conclusions: We have developed and validated a method to isolate rare CTCs and profile them via cDNA microarray analysis. In addition, our gene expression analyses of CTC further provide evidence to the malignant nature of these cells. Further expression profiling of CTC may yield insights into their phenotype, pathophysiology and potential as biomarkers. [Table: see text]

scholarly journals Identification of genes and pathways related to lymphovascular invasion in breast cancer patients: A bioinformatics analysis of gene expression profiles

Tumor Biology ◽  
2017 ◽  
Vol 39 (6) ◽  
pp. 101042831770557 ◽  
Author(s):  
Sukhontip Klahan ◽  
Henry Sung-Ching Wong ◽  
Shih-Hsin Tu ◽  
Wan-Hsuan Chou ◽  
Yan-Feng Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Lymphovascular Invasion ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Breast Cancer Patients

scholarly journals TWIST1 Gene expression as a biomarker for predicting primary doxorubicin resistance in breast cancer

2019 ◽  
Vol 22 (2) ◽  
pp. 25-30
Author(s):  
S Demir ◽  
MH Müslümanoğlu ◽  
M Müslümanoğlu ◽  
S Başaran ◽  
ZZ Çalay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Cancer Patients ◽  
Breast Tumors ◽  
Chemotherapeutic Agents ◽  
Primary Breast Tumor ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Transcription Factor Expression

AbstractDoxorubicin is one of the most commonly used chemotherapeutic agents for adjuvant chemotherapy of breast cancer. In the studies focused on finding biomarkers to predict the response of the patients and tumors to the drugs used, the Twist transcription factor has been suggested as a candidate biomarker for predicting chemo-resistance of breast tumors. In this study, we aimed to investigate the relationship between TWIST transcription factor expression and the effectiveness of doxorubicin treatment on directly taken primary tumor samples from chemotherapy-naive breast cancer patients. Twenty-six primary breast tumor samples taken from 26 different breast cancer patients were included in this study. Adenosine triphosphate tumor chemo-sensitivity assay (ATP-TCA) has been used to determine tumor response to doxorubicin and real-time reverse-transcription polymerase chain reaction (RT-PCR) was used for analyzing the TWIST1 gene expression of tumors. There was a significant difference in TWIST gene expression between responder and non responder tumors (p <0.05). The TWIST gene expression of the drug-resistant group was higher than the responsive group. This difference was not dependent on the histopathological features of tumors. In conclusion, compatible with earlier studies that have been performed with cell lines, the current study supports the role of higher TWIST gene expression as a biomarker for predicting the response of breast tumors to chemo-therapeutic agent doxorubicin.

IS tRNA DRIVING BREAST CANCER PROGRESSION?

2019 ◽  
Author(s):  
Zil-e- Rubab
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Developing Countries ◽  
Molecular Mechanism ◽  
Cancer Progression ◽  
Critical Review ◽  
Driving Forces ◽  
Treatment Modalities ◽  
Critical Research ◽  
Research Article

This critical research periodical is mainly based on critical review of research article titled ‘Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression published in Cell by Goodarzi et al1. According to Globocan, 2008 report2, breast is among the leading site of new cancer cases and deaths (691,300/268,900) in females of developing countries and second leading site in USA (Globocan, 2012)3. The extensive research is in progress on different aspects of molecular mechanism of driving forces and different treatment modalities to ease this burden. The above mentioned research article is also part of this effort.

Overexpression of microRNA-21 in the Serum of Breast Cancer Patients

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 58-63
Author(s):  
Batool Savari ◽  
Sohrab Boozarpour ◽  
Maryam Tahmasebi-Birgani ◽  
Hossein Sabouri ◽  
Seyed Mohammad Hosseini
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Tumor Resection ◽  
Tumor Grade ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Post Surgery ◽  
Polymerase Chain

Background: Breast cancer is the most common cancer diagnosed in women worldwide. So it seems that there's a good chance of recovery if it's detected in its early stages even before the appearances of symptoms. Recent studies have shown that miRNAs play an important role during cancer progression. These transcripts can be tracked in liquid samples to reveal if cancer exists, for earlier treatment. MicroRNA-21 (miR-21) has been shown to be a key regulator of carcinogenesis, and breast tumor is no exception. Objective: The present study was aimed to track the miR-21 expression level in serum of the breast cancer patients in comparison with that of normal counterparts. Methods: Comparative real-time polymerase chain reaction was applied to determine the levels of expression of miR-21 in the serum samples of 57 participants from which, 42 were the patients with breast cancer including pre-surgery patients (n = 30) and post-surgery patients (n = 12), and the others were the healthy controls (n = 15). Results: MiR-21 was significantly over expressed in the serum of breast cancer patients as compared with healthy controls (P = 0.002). A significant decrease was also observed following tumor resection (P < 0.0001). Moreover, it was found that miR-21 overexpression level was significantly associated with tumor grade (P = 0.004). Conclusion: These findings suggest that miR-21 has the potential to be used as a novel breast cancer biomarker for early detection and prognosis, although further experiments are needed.

scholarly journals Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kalifa Manjang ◽  
Shailesh Tripathi ◽  
Olli Yli-Harja ◽  
Matthias Dehmer ◽  
Galina Glazko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Progression ◽  
Disease Etiology ◽  
Signature Genes ◽  
Biological Meaning ◽  
Gene Sets ◽  
Breast Cancer Outcome ◽  
Biological Interpretation ◽  
Pathological Behavior

AbstractThe identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large number of breast cancer signatures that such an implication is not justified. Our approach eliminates systematically all traces of biological meaning of signature genes and shows that among the remaining genes, surrogate gene sets can be formed with indistinguishable prognostic prediction capabilities and opposite biological meaning. Hence, our results demonstrate that none of the studied signatures has a sensible biological interpretation or meaning with respect to disease etiology. Overall, this shows that prognostic signatures are black-box models with sensible predictions of breast cancer outcome but no value for revealing causal connections. Furthermore, we show that the number of such surrogate gene sets is not small but very large.

scholarly journals Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xu Yang ◽  
Geng-Xi Cai ◽  
Bo-Wei Han ◽  
Zhi-Wei Guo ◽  
Ying-Song Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cell Receptor ◽  
Chemotherapy Response ◽  
Breast Cancer Patients ◽  
Plasma Dna ◽  
Transcription Start Sites ◽  
Response To Chemotherapy

AbstractGene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.

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