Gene expression-based predictors of chemotherapy response in basal-like breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10500-10500 ◽  
Author(s):  
Aleix Prat ◽  
Ana Lluch ◽  
Joan Albanell ◽  
Cheng Fang ◽  
Jose Ignacio Chacon Lopez-Muniz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Gene Signature ◽  
High Expression ◽  
Chemotherapy Response ◽  
Biological Processes ◽  
Expression Of Genes ◽  
Basal Like Breast Cancer

10500 Background: The Basal-like subtype is generally associated with high chemo-sensitivity, but not all tumors respond and/or benefit to the same extend. In this study, we sought to identify gene expression predictors of neoadjuvant chemotherapy sensitivity in Basal-like breast cancer. Methods: Expression of 542 genes was measured using the Nanostring nCounter platform from 69 FFPE pre-treated samples of the GEICAM/2006-03 phase II trial, which were treated with epirrubicin/cyclophosphamide followed by docetaxel+/-carboplatin. Research-based PAM50 and Claudin-low predictors were also evaluated. The association between response (Miller-Payne criteria) and gene/signature expression was assessed by multivariable ordinal logistic regression. Significant findings were evaluated in 109 independent triple-negative and Basal-like tumors treated with anthracycline/taxane-based chemotherapy (Hatzis et al.). Finally, interaction tests were performed to identify genes/signatures associated with carboplatin response. Results: In GEICAM/2006-03, 61/69 (88%) tumors were identified as Basal-like by PAM50. High correlation to the Basal-like centroid, or high expression of proliferation-related genes (i.e. FANCA), were found to be significantly associated with high chemo-sensitivity, whereas high expression of genes associated with mesenchymal/stem cell biological processes (i.e. SNAI1 and IL6) and/or luminal differentiation (i.e. MUC1 and FOXA1) were significantly associated with chemo-resistance; similar findings were observed in Hatzis et al. Finally, high expression of genes associated with proliferation/DNA-repair (i.e. ATR) and tight junctions (i.e. CLDN3/4/7) were found associated with carboplatin response, whereas expression of the Claudin-low signature was found associated with carboplatin resistance. Conclusions: High expression of Basal-like and/or proliferation-related genes and low expression of luminal/mesenchymal/stem cell-like biological processes were consistently identified as predictive of chemotherapy response. Our data suggests that gene expression profiling might help shed light into the biological and clinical heterogeneity of Basal-like breast cancer.

scholarly journals Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sarah M. Bernhardt ◽  
Pallave Dasari ◽  
Danielle J. Glynn ◽  
Lucy Woolford ◽  
Lachlan M. Moldenhauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Menstrual Cycle ◽  
Recurrence Score ◽  
Gene Signature ◽  
Ovarian Cycle ◽  
Oncotype Dx ◽  
Mammary Tumours ◽  
Er Positive ◽  
The Impact

Abstract Background The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p ≤ 0.05) and a significant increase in 21-gene recurrence score (21.8 ± 2.4; mean ± SEM) compared to tumours dissected at estrus (15.5 ± 1.9; p = 0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p < 0.001) and invasion-group (p = 0.01) genes, and increased 21-gene recurrence score (p = 0.01). No correlation between ER, PR, HER2, and KI67 protein abundance measured by Western blot and abundance of mRNA for the corresponding gene was observed, suggesting that gene expression is more susceptible to hormone-induced fluctuation compared to protein expression. Conclusions Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature in Mmtv-Pymt murine mammary tumours. Further studies are required to determine whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage.

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.

scholarly journals Melatonin promotes bone marrow mesenchymal stem cell osteogenic differentiation and prevents osteoporosis development through modulating circ_0003865 that sponges miR-3653-3p

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xudong Wang ◽  
Taiqiu Chen ◽  
Zhihuai Deng ◽  
Wenjie Gao ◽  
Tongzhou Liang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Osteogenic Differentiation ◽  
Luciferase Reporter ◽  
Specific Gene ◽  
Biological Processes ◽  
Alizarin Red ◽  
Qrt Pcr ◽  
Dual Luciferase Reporter Assay

Abstract Background Little is known about the implications of circRNAs in the effects of melatonin (MEL) on bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation and osteoporosis (OP) progression. The aim of our study was to investigate circRNAs in MEL-regulated BMSC differentiation and OP progression. Methods BMSC osteogenic differentiation was measured by qRT-PCR, western blot (WB), Alizarin Red, and alkaline phosphatase (ALP) staining. Differential circRNA and mRNA profiles of BMSCs treated by MEL were characterized by deep sequencing, followed by validation using RT-PCR, Sanger sequencing, and qRT-PCR. Silencing and overexpression of circ_0003865 were conducted for functional investigations. The sponged microRNAs and targeted mRNAs were predicted by bioinformatics and validated by qRT-PCR, RNA pull-down, and dual-luciferase reporter assay. The function of miR-3653-3p and circ_0003865/miR-3653-3p/growth arrest-specific gene 1 (GAS1) cascade was validated for the osteogenic differentiation of BMSCs by CCK-8, qRT-PCR, WB, Alizarin Red, and ALP staining. The effects of circ_0003865 on OP development were tested in murine OP model. Results MEL promoted osteogenic differentiation of BMSCs. RNA sequencing revealed significant alterations in circRNA and mRNA profiles associated with multiple biological processes and signaling pathways. Circ_0003865 expression in BMSCs was significantly decreased by MEL treatment. Silencing of circ_0003865 had no effect on proliferation while promoted osteogenic differentiation of BMSCs. Overexpression of circ_0003865 abrogated the promotion of BMSC osteogenic differentiation induced by MEL, but proliferation of BMSCs induced by MEL had no change whether circ_0003865 was overexpression or not. Furthermore, circ_0003865 sponged miR-3653-3p to promote GAS1 expression in BMSCs. BMSC osteogenic differentiation was enhanced by miR-3653-3p overexpression while BMSC proliferation was not affected. By contrast, miR-3653-3p silencing mitigated the promoted BMSC osteogenic differentiation caused by circ_0003865 silencing, but had no effect on proliferation. Finally, circ_0003865 silencing repressed OP development in mouse model. Conclusion MEL promotes BMSC osteogenic differentiation and inhibits OP pathogenesis by suppressing the expression of circ_0003865, which regulates GAS1 gene expression via sponging miR-3653-3p.

Gene Expression–Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial

2021 ◽  
Vol 27 (8) ◽  
pp. 2148-2158
Author(s):  
Karolina Edlund ◽  
Katrin Madjar ◽  
Antje Lebrecht ◽  
Bahriye Aktas ◽  
Henryk Pilch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Neoadjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Chemotherapy Response

scholarly journals A clinically relevant gene signature in triple negative and basal-like breast cancer

2011 ◽  
Vol 13 (5) ◽  
Author(s):  
Achim Rody ◽  
Thomas Karn ◽  
Cornelia Liedtke ◽  
Lajos Pusztai ◽  
Eugen Ruckhaeberle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Gene Signature ◽  
Basal Like Breast Cancer ◽  
Relevant Gene

scholarly journals Mesenchymal Stem Cell-Mediated Delivery of the Sodium Iodide Symporter Supports Radionuclide Imaging and Treatment of Breast Cancer

Stem Cells ◽  
2011 ◽  
Vol 29 (7) ◽  
pp. 1149-1157 ◽  
Author(s):  
Roisin M. Dwyer ◽  
James Ryan ◽  
Ronan J. Havelin ◽  
John C. Morris ◽  
Brian W. Miller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Radionuclide Imaging ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter

scholarly journals Response to FEC Chemotherapy and Oncolytic HSV-1 Is Associated with Macrophage Polarization and Increased Expression of S100A8/A9 in Triple Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5590
Author(s):  
Alyssa Vito ◽  
Nader El-Sayes ◽  
Omar Salem ◽  
Yonghong Wan ◽  
Karen L. Mossman
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Macrophage Polarization ◽  
Gene Signature ◽  
Immune Checkpoint Blockade ◽  
Differential Gene ◽  
Microarray Analyses ◽  
Tumor Cell Killing

The era of immunotherapy has seen an insurgence of novel therapies driving oncologic research and the clinical management of the disease. We have previously reported that a combination of chemotherapy (FEC) and oncolytic virotherapy (oHSV-1) can be used to sensitize otherwise non-responsive tumors to immune checkpoint blockade and that tumor-infiltrating B cells are required for the efficacy of our therapeutic regimen in a murine model of triple-negative breast cancer. In the studies herein, we have performed gene expression profiling using microarray analyses and have investigated the differential gene expression between tumors treated with FEC + oHSV-1 versus untreated tumors. In this work, we uncovered a therapeutically driven switch of the myeloid phenotype and a gene signature driving increased tumor cell killing.

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