CWRU Circulating miRNAs in Breast Cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Thompson Cheryl
PROVIDER: S-ECPF-GEOD-41526 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Great improvement has been made in the diagnosis and therapy of breast cancer patients. However, the identification of biomarkers for early diagnosis, prognosis, therapy assessment and monitoring, including drug resistance and the early detection of micro-metastases, is still lacking. Recently, circulating microRNAs (miRNAs), circulating freely in the blood stream or entrapped in extracellular vesicles (EVs), have been shown to have a potential diagnostic, prognostic or predictive power. In this review, recent findings are summarized, both at a preclinical and clinical level, related to miRNA applicability in the context of breast cancer. Different aspects, including clinical and technical challenges, are discussed, describing the potentialities of miRNA use in breast cancer. Even though more methodological standardized studies conducted in larger and selected patient cohorts are needed to support the effective clinical utility of miRNA as biomarkers, they could represent novel and accessible tools to be transferred into clinical practice.
| S-EPMC9101355 | biostudies-literature
Project description:Breast cancer is a common disease with distinct tumor subtypes which can be phenotypically characterized by estrogen receptor, progesterone receptor and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression. Altered miRNA expression has been demonstrated in a variety of cancer states to date presenting the potential for exploitation as cancer specific biomarkers. Blood presents an attractive medium biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A (ER+PR+HER2/neu-) breast cancer and their effectiveness as oncologic biomarkers in the clinical setting. Blood samples were prospectively collected from consenting patients with Luminal A breast cancer (n=10) and controls (n=10). RNA was extracted, reverse transcribed and subjected to microarray analysis (n=10 Luminal A; n=10 Control). Differentially expressed miRNAs were identified by artificial neural network (ANN) data-mining algorithms. Ethical approval was granted by the Clinical Research Ethics Committee, Galway Roscommon University Hospital Group. Written informed consent was obtained from all study participants. Blood samples were prospectively collected from 20 women; this included 10 consecutive women with a new diagnosis of Luminal A breast cancer and 10 healthy control participants. Luminal A status was confirmed with immunohistochemistry and fluorescence in situ hybridization (FISH). The blood samples for the healthy control group were collected from women residing in the same catchment area as the cancer cases. These women had no personal history of malignancy and no current inflammatory or infectious condition. Venous non-fasting whole blood samples were collected in BD vacutainers ® containing 18mg dipotassium EDTA anticoagulant (BD-Plymouth, PL6 7BP, UK). Total RNA was extracted from blood (1ml) using TRI Reagent BD (Molecular Research Centre, Inc). RNA concentration and integrity were evaluated by NanoDrop spectrophotometry (NanoDrop ND-1000 Technologies Inc., DE, USA) and Agilent Bioanalyzer RNA 6000 NanoChip Kit Series II (Agilent Technologies, Germany) analysis, respectively. MiRNA microarray profiling Expression profiling of circulating miRNAs was performed using TaqMan miRNA arrays and assays in accordance with the manufacturer’s instructions (Taqman Low Density Array Human microRNA Card A and Card B, Applied Biosystems, Foster City, CA, USA). In short, total RNA was reverse transcribed using Megaplex primer pool A (Applied Biosystems) which contained sequence-specific primers for 381 specific miRNAs plus 3 controls (pool A). An additional panel of 384 miRNAs (381 miRNAs and 3 controls, pool B) was performed on a subset of 4 cancers and 4 controls. Real-time quantitative PCR was performed for 667 miRNAs, using A and B microfluidic cards, each containing primers and probes for 381 specific miRNAs plus 3 controls and thermal-cycled on an Applied Biosystems 7900HT instrument. The TLDA cards contain three endogenous controls (RNU44, RNU48 and MammU6 which is repeated four times on each card). Each card also contains a negative control, an assay unrelated to any human species, ath-miR-159a.
| S-ECPF-GEOD-46355 | biostudies-other
Project description:Prolonged life expectancy in humans has been accompanied by an increase in the prevalence of cancers. Breast cancer (BC) is the leading cause of cancer-related deaths. It accounts for one-fourth of all diagnosed cancers and affects one in eight females worldwide. Given the high BC prevalence, there is a practical need for demographic screening of the disease. In the present study, we re-analyzed a large microRNA (miRNA) expression dataset (GSE73002), with the goal of optimizing miRNA biomarker selection using neural network cascade (NNC) modeling. Our results identified numerous candidate miRNA biomarkers that are technically suitable for BC detection. We combined three miRNAs (miR-1246, miR-6756-5p, and miR-8073) into a single panel to generate an NNC model, which successfully detected BC with 97.1% accuracy in an independent validation cohort comprising 429 BC patients and 895 healthy controls. In contrast, at least seven miRNAs were merged in a multiple linear regression model to obtain equivalent diagnostic performance (96.4% accuracy in the independent validation set). Our findings suggested that suitable modeling can effectively reduce the number of miRNAs required in a biomarker panel without compromising prediction accuracy, thereby increasing the technical possibility of early detection of BC.
| S-EPMC5875392 | biostudies-literature
Project description:Study investigating the role of miRNAs in breast cancer detection miRNA extracted from plasma on 20 breast cancer patients, 20 controls, 20 post-resection breast cancer patients and 10 lung/colorectal cancer patients, miRNA quanitification using Illumina microarray
2012-10-13 | E-GEOD-41526 | biostudies-arrayexpress
Project description:PurposeTo build models combining circulating microRNAs (miRNAs) able to identify women with breast cancer as well as different types of breast cancer, when comparing with controls without breast cancer.MethodmiRNAs analysis was performed in two phases: screening phase, with a total n = 40 (10 controls and 30 BC cases) analyzed by Next Generation Sequencing, and validation phase, which included 131 controls and 269 cases. For this second phase, the miRNAs were selected combining the screening phase results and a revision of the literature. They were quantified using RT-PCR. Models were built using logistic regression with LASSO penalization.ResultsThe model for all cases included seven miRNAs (miR-423-3p, miR-139-5p, miR-324-5p, miR-1299, miR-101-3p, miR-186-5p and miR-29a-3p); which had an area under the ROC curve of 0.73. The model for cases diagnosed via screening only took in one miRNA (miR-101-3p); the area under the ROC curve was 0.63. The model for disease-free cases in the follow-up had five miRNAs (miR-101-3p, miR-186-5p, miR-423-3p, miR-142-3p and miR-1299) and the area under the ROC curve was 0.73. Finally, the model for cases with active disease in the follow-up contained six miRNAs (miR-101-3p, miR-423-3p, miR-139-5p, miR-1307-3p, miR-331-3p and miR-21-3p) and its area under the ROC curve was 0.82.ConclusionWe present four models involving eleven miRNAs to differentiate healthy controls from different types of BC cases. Our models scarcely overlap with those previously reported.
| S-EPMC10625260 | biostudies-literature
Project description:Study investigating the role of miRNAs in breast cancer detection
2012-10-13 | GSE41526 | GEO
Project description:BackgroundTriple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer in women globally. This subtype often has early and high recurrence rates resulting in poor survival, partially due to lack of targeted therapies. Therefore, there is an urgent need to identify TNBC-specific biomarkers for early diagnosis and treatment monitoring, and to develop more effective targeted therapy.MethodsBy using miRCURY LNA array platform, we compared the differential miRNA expressions in plasma of patient with TNBC (n=5) and non-TNBC (n=5), as well as healthy controls (n=5). Potential miRNAs were then validated in a large cohort of patients by real-time PCR.ResultsTen putative miRNAs from the microarray data that differentially expressed between non-TNBC and healthy controls were identified. In the screening phase (n=90), we selected five miRNAs (miR-92a-3p, miR-342-3p, miR-16, miR-21 and miR-199a-5p) that could discriminate TNBC from non-TNBC for further validation. Results showed that miR-16, miR-21 and miR-199a-5p were underexpressed in TNBC when compared with non-TNBC, and were further validated in a large cohort (n=252). In addition, post-operative plasma levels of miR-16, miR-21 and miR-199a-5p were significantly restored when compared with pre-operative plasma of TNBC. Plasma miR-199a-5p expression in TNBC had significant difference when compared with non-TNBC and healthy controls, the receiver-operator characteristics curve analysis revealed the highest area under curve (AUC=0.8838) among all. The expression levels were associated with TNM stage and tumour subtypes.ConclusionsOur data suggest that miR-199a-5p could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC.
| S-EPMC4647231 | biostudies-literature
Project description:Analysis of the levels of circulating miRNAs from women with early stage breast cancer and matched healthy controls. miRNAs in plasma samples from 20 women with early stage breast cancer (10 Caucasian American and 10 African American) compared with 20 matched healthy controls (10 Caucasian American and 10 African American).
| S-ECPF-GEOD-22981 | biostudies-other
Project description:The aim of this study was to identify new disease-related circulating miRNAs with high diagnostic accuracy for breast cancer (BC) and to correlate their deregulation with the morpho-functional characteristics of the tumour, as assessed in vivo by positron emission tomography/magnetic resonance (PET/MR) imaging. A total of 77 untreated female BC patients underwent same-day PET/MR and blood collection, and 78 healthy donors were recruited as negative controls. The expression profile of 84 human miRNAs was screened by using miRNA PCR arrays and validated by real-time PCR. The validated miRNAs were correlated with the quantitative imaging parameters extracted from the primary BC samples. Circulating miR-125b-5p and miR-143-3p were upregulated in BC plasma and able to discriminate BC patients from healthy subjects (miR-125-5p area under the receiver operating characteristic ROC curve (AUC) = 0.85 and miR-143-3p AUC = 0.80). Circulating CA15-3, a soluble form of the transmembrane glycoprotein Mucin 1 (MUC-1) that is upregulated in epithelial cancer cells of different origins, was combined with miR-125b-5p and improved the diagnostic accuracy from 70% (CA15-3 alone) to 89% (CA15-3 plus miR-125b-5p). MiR-143-3p showed a strong and significant correlation with the stage of the disease, apparent diffusion coefficient (ADCmean), reverse efflux volume transfer constant (Kepmean) and maximum standardized uptake value (SUVmax), and it might represent a biomarker of tumour aggressiveness. Similarly, miR-125b-5p was correlated with stage and grade 2 but inversely correlated with the forward volume transfer constant (Ktransmean) and proliferation index (Ki67), suggesting a potential role as a biomarker of a relatively more favourable prognosis. In situ hybridization (ISH) experiments revealed that miR-143-3p was expressed in endothelial tumour cells, miR-125-5p in cancer-associated fibroblasts, and neither in epithelial tumour cells. Our results suggested that miR-125-5p and miR-143-3p are potential biomarkers for the risk stratification of BC, and Kaplan-Maier plots confirmed this hypothesis. In addition, the combined use of miR-125-b-5p and CA15-3 enhanced the diagnostic accuracy up to 89%. This is the first study that correlates circulating miRNAs with in vivo quantified tumour biology through PET/MR biomarkers. This integration elucidates the link between the plasmatic increase in these two potential circulating biomarkers and the biology of untreated BC. In conclusion, while miR-143-3b and miR-125b-5p provide valuable information for prognosis, a combination of miR-125b-5p with the tumour marker CA15-3 improves sensitivity for BC detection, which warrants consideration by further validation studies.
| S-EPMC6628327 | biostudies-literature
Project description:The effective management of patients with breast cancer (BC) depends on the early diagnosis of the disease. Currently, BC diagnosis is based on diagnostic imaging and biopsy, while the use of non-invasive circulating biomarkers for diagnosis remains an unmet need. Among the plethora of proposed non-invasive biomarkers, circulating microRNAs (miRNAs) have been considered promising diagnostic molecules because they are very stable in biological fluids and easily detectable. Although the discovery of miRNAs has opened a new avenue for their clinical application, the clinical translatability of these molecules remains unclear. This review analyses the role of circulating miRNAs as BC diagnostic biomarkers and focuses on two essential requirements to evaluate their clinical validity: i) Specificity and ii) consistent expression between the blood and tissue. These two issues were analyzed in depth using the Human miRNA Disease Database (HMDD v3.0) and the free search engine PubMed. One hundred and sixty three BC-associated miRNAs were selected and analyzed for their specificity among all human pathologies that shared deregulation (291) and consistent expression in the bloodstream and the tissue. In addition, we provide an overview of the current clinical trials examining miRNAs in BC. In conclusion, we highlight pitfalls in the translatability of circulating miRNAs into clinical practice due to the lack of specificity and a consistent expression pattern between the tissue and blood.
| S-EPMC6678980 | biostudies-literature