Tumor circadian clock strength influences metastatic potential and predicts patient prognosis in Luminal A breast cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE233242 | GEO | 2024/01/26
REPOSITORIES: GEO
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Project description:Background: Luminal B cancers show much worse outcomes compared to luminal A. This present study aims to screen key lncRNAs and mRNAs correlated with luminal-B breast cancer. Methods: Luminal-B breast cancer tissue samples and adjacent tissue samples were obtained from 4 patients with luminal-B breast cancer. To obtain differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between luminal-B breast cancer tumor tissues and adjacent tissues, RNA-sequencing and bioinformatics analysis were performed. Functional annotation of DEmRNAs and protein-protein interaction networks (PPI) construction were performed. DEmRNAs transcribed within a 100kb window up- or down-stream of DElncRNAs were searched, which were defined as cis nearby-targeted DEmRNAs of DElncRNAs. DElncRNA-DEmRNA co-expression networks were performed. Results: A total of 1178 DEmRNAs and 273 DElncRNAs between luminal-B breast cancer tumor tissues and adjacent tissues were obtained. Hematopoietic cell lineage, Cytokine-cytokine receptor interaction, Cell adhesion molecules (CAMs) and Primary immunodeficiency were significantly enriched KEGG pathways in luminal-B breast cancer. FN1, EGFR, JAK3, TUBB3 and PTPRC were five hub proteins of the PPI networks. A total of 99 DElncRNAs-nearby-targeted DEmRNA pairs and 1878 DElncRNA-DEmRNA co-expression pairs were obtained. Conclusion: This study determined key genes and lncRNAs involved in luminal-B breast cancer, which expected to present a new avenue for the diagnosis and treatment of luminal-B breast cancer.
2020-04-14 | GSE139274 | GEO
Project description:Purpose:The Vimentin gene plays a pivotal role in epithelial-to-mesenchymal transition (EMT) and is known to be over-expressed in the prognostically poor basal-like breast cancer subtype. Recent studies have reported Vimentin DNA methylation in association with poor clinical outcomes in other solid tumors, but not in breast cancer. We therefore quantified Vimentin DNA methylation in breast tumors and matched normal pairs in association with gene expression and survival in a cohort of 83 breast cancer patients. Materials and Methods:Vimentin methylation was quantified in 14 breast cell lines, 83 breast tumors, and 57 matched normal pairs using MALDI-TOF mass spectrometry. Gene expression data via qRT-PCR in cell lines, and oligo microarray data from breast tissues was correlated with percent methylation in the Vimentin promoter. A threshold of 20 percent average methylation was set for bivariate and multivariate tests of association between methylation and tumor subtype, tumor histopathology, and survival. Results:Vimentin was differentially methylated in luminal breast cancer cell lines, and in luminal A, luminal B and HER2+ breast tumor subtypes, but was rare in basal-like cell lines and tumors. Increased methylation was strongly correlated with decreased mRNA expression in cell lines, and had a moderate inverse correlation in breast tumors. Importantly, Vimentin methylation predicted poor overall survival independent of race, subtype, stage, nodal status or estrogen receptor positivity. Conclusion:Vimentin methylation predicts overall survival in breast cancer patients and holds promise as a prognostic biomarker for guiding treatment and prophylaxis. reference x sample
2013-02-19 | E-GEOD-35629 | biostudies-arrayexpress
Project description:Purpose:The Vimentin gene plays a pivotal role in epithelial-to-mesenchymal transition (EMT) and is known to be over-expressed in the prognostically poor basal-like breast cancer subtype. Recent studies have reported Vimentin DNA methylation in association with poor clinical outcomes in other solid tumors, but not in breast cancer. We therefore quantified Vimentin DNA methylation in breast tumors and matched normal pairs in association with gene expression and survival in a cohort of 83 breast cancer patients. Materials and Methods:Vimentin methylation was quantified in 14 breast cell lines, 83 breast tumors, and 57 matched normal pairs using MALDI-TOF mass spectrometry. Gene expression data via qRT-PCR in cell lines, and oligo microarray data from breast tissues was correlated with percent methylation in the Vimentin promoter. A threshold of 20 percent average methylation was set for bivariate and multivariate tests of association between methylation and tumor subtype, tumor histopathology, and survival. Results:Vimentin was differentially methylated in luminal breast cancer cell lines, and in luminal A, luminal B and HER2+ breast tumor subtypes, but was rare in basal-like cell lines and tumors. Increased methylation was strongly correlated with decreased mRNA expression in cell lines, and had a moderate inverse correlation in breast tumors. Importantly, Vimentin methylation predicted poor overall survival independent of race, subtype, stage, nodal status or estrogen receptor positivity. Conclusion:Vimentin methylation predicts overall survival in breast cancer patients and holds promise as a prognostic biomarker for guiding treatment and prophylaxis.
2013-02-19 | GSE35629 | GEO
Project description:In-depth clinical proteomic analysis of laser-microdissected HOT lesions of five luminal B breast cancer Ki-67 high subtype.
2020-10-12 | PXD021912 | JPOST Repository
Project description:Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative breast cancer (TNBC), is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thus a biological basis for the further investigation of immunotherapeutic strategies is missing. By using high-dimensional single-cell technologies, we identified heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells infiltrating luminal-like tumors. We defined that a subset of CD127- CD39hi Trm cells is preferentially present in the tumor compared to the adjacent normal breast tissue or peripheral blood, displayed enhanced effector functions compared to the CD127+ CD39lo Trm counterpart, and was specifically associated with positive prognosis. Nevertheless, the prognostic benefit was lost in the presence of highly-suppressive CCR8hi ICOShi IRF4+ effector Tregs. Our results suggest that combinatorial strategies aiming at boosting Trm function while relieving from Treg-mediated immunosuppression are needed to achieve proper tumor control in luminal-like BCs.
2021-10-13 | GSE154842 | GEO
Project description:LSD1 (KDM1A) is a histone demethylase that plays both oncogenic and tumor suppressor roles in breast cancer. However, the exact contexts under which it plays these opposite roles remain largely elusive. By characterizing its role in normal and cancerous luminal mammary epithelial cells (MECs), here we show that LSD1 is essential for maintaining differentiation and survival of luminal cells. LSD1-inhibition by both genetic and pharmacological approaches increases invasion of luminal breast cancer cells. Mechanistically, we find LSD1 interacts with GATA3 and their common target genes are highly related to breast cancer. LSD1 positively regulates GATA3 expression and represses that of TRIM37, a histone H2A ubiquitin ligase and breast cancer oncoprotein. LSD1-loss leads to reduced expression of several cell junction genes (e.g., CDH1, VCL, CTNNA1), possibly via TRIM37-mediated repression. Collectively, our data suggest LSD1 largely plays a tumor suppressor role in luminal breast cancer and the increased MEC invasiveness associated with LSD1-inhibition can be blocked via TRIM37-inhibition.
2019-08-16 | GSE95165 | GEO
Project description:Purpose In breast cancer, specific aberrant methylation patterns have been associated with different BC histologic and molecular subtypes and data suggest that DNA methylation profiles may play an important role in the development and progression of distinct breast subtypes. However, the epigenome of the newly defined luminal B and luminal B-HER2 positive breast cancers has not yet been characterized. Therefore the main goal of the current study is to deciphered the aberrant DNA methylation profiles associated with these breast cancer subtypes. Experimental Design 29 luminal subtype breast cancer samples along with 8 control tissue were epigenetically interrogated using the HumanMethylation27 DNA Analysis BeadChip. Results Luminal B-HER2 + subtype displays the most aggressive phenotype and shows the highest number of aberrantly methylated CpG markers. On the other hand, the luminal B subtype harbours an heterogeneous DNA methylation profile that seems to be half way between the luminal A and luminalB-HER2+ subtypes. Conclusions The heterogeneous epigenetic and genetic profile of the luminal B subtype, might indicate that a further stratification has to be done for this specific breast cancer subtype.
2016-12-18 | GSE73808 | GEO
Project description:We developed two novel sperm epigenetic clocks by applying Super Learner, an ensemble machine learning algorithm, to predict age from sperm EPIC array DNA methylation data via individual CpG sites and differentially methylated regions (DMRs). Overall, our cox model showed that one-year increase in our developed sperm epigenetic age (SEA) was associated with up to 15% reduction in couples time-to-pregnancy (TTP).
2022-07-06 | GSE185445 | GEO
Project description:Secreted proteins and transmembrane proteins with extracellular domains are frequently glycosylated; this group of proteins includes those that participate in the various intercellular junctions and signaling pathways of an epithelium. In this study we characterized the differences in glycoprotein expression between claudin-low and other breast cell lines using a dataset of 26 breast cell lines in which the glycoproteins were identified and quantitated by liquid chromatography/ tandem mass spectrometry. Our goals are to characterize the glycoproteome of a set of claudin-low lines, compare them to basal, luminal and non-malignant cells and to identify drugs that may be especially effective on these cell lines. These seven luminal malignant breast cells (BT474, HCC1428, MCF7, SKBR3, SUM185PE, T47D and ZR751) data are a part of 26 breast cell lines we analyzed.
2017-03-22 | PXD005390 | Pride
Project description:The transcription factor c-Myb has been well characterized as an oncogene in several human tumor types, and its expression in the hematopoietic stem/progenitor cell population is essential for proper hematopoiesis. However, the role of c-Myb in mammopoeisis and breast tumorigenesis is poorly understood, despite its high expression in the majority of breast cancer cases (60-80%). We find that c-Myb high expression in human breast tumors correlates with the luminal/ER+ phenotype and a good prognosis. RNAi knock-down of endogenous c-Myb levels in the MCF7 luminal breast tumor cell line increases tumorigenesis both in vitro and in vivo, suggesting a tumor suppressor role in luminal breast cancer. We created a mammary-derived c-Myb expression signature and found it to be highly correlated with a published mature luminal mammary cell signature and least correlated with a mammary stem/progenitor lineage gene signature. These data describe, for the first time, a tumor suppressor role for the c-Myb proto-oncogene in breast cancer that has implications for understanding luminal tumorigenesis and for guiding treatment. refXsample
2010-10-15 | E-GEOD-21371 | biostudies-arrayexpress