Project description:microRNAs (miRNAs) are short, non-coding RNA molecules that act as regulators of gene expression. Circulating blood miRNAs offer great potential as cancer biomarkers. The objective of the study was to correlate the differential expression of miRNAs in tissue and blood in the identification of biomarkers for early detection of colorectal cancer (CRC).
Project description:microRNAs (miRNAs) are short, non-coding RNA molecules that act as regulators of gene expression. Circulating blood miRNAs offer great potential as cancer biomarkers. The objective of the study was to correlate the differential expression of miRNAs in tissue and blood in the identification of biomarkers for early detection of colorectal cancer (CRC). miRNA biomarker discovery via miRNA array profiling using paired cancer tissues (n = 30) and blood samples (CRC, n = 42; control, n = 18).
Project description:We hypothesized that circulating miRNAs could work as biomarkers for early detection of breast cancer brain metastasis (BCBM), and their targets could constitute new targets for modulation. We used a mouse model of BCBM and Next-Generation Sequencing to establish the circulating miRNAs alterations along brain metastasis development and performed bioinformatics analysis to identify their targets with relevance in the metastatic process. We additionally analyzed human resected brain metastasis of breast cancer patients for target’s expression validation. In our mouse model, we observed a deregulation of circulating miRNAs profile during BCBM progression, with a downregulation of miR-802-5p and miR-194-5p in plasma prior to brain metastases detection. The transcription factor myocyte enhancer factor 2C (MEF2C), was identified as a target for both miRNAs, and its expression was increasingly observed in malignant cells along brain metastasis development. Its upregulation was also observed in peritumoral astrocytes and in human BCBM. Collectively, downregulation of circulating miR-802-5p and miR-194-5p appear as precocious biomarkers for BCBM and MEF2C emerges as a new player and a potential target for modulation.
Project description:Circulating microRNAs (miRNAs) are promising biomarkers for the early detection of cancers. This assay aimed to address potential circulating miRNAs to monitor the progression from Barrett’s esophagus to esophageal adenocarcinoma (EAC).
Project description:Due to their role in tumorigenesis and remarkable stability in body fluids, microRNAs (miRNAs) are emerging as a promising diagnostic tool. The aim of this study was to identify tumor miRNA signatures for the discrimination of breast cancer and the intrinsic molecular subtypes, and the study in plasma of the status of the most significant ones in order to identify potential circulating biomarkers for breast cancer detection.
Project description:Circulating microRNAs (c-miRNAs) have emerged as measurable biomarkers (liquid biopsies) for cancer detection. The goal of our study was to identify novel biomarkers to predict long-term breast cancer risk in cancer-free women. We evaluated the ability of c-miRNAs to identify women most likely to develop breast cancer by profiling miRNA from serum obtained long before diagnosis. 24 breast cancer cases and controls (matched for risk and age) were identified from women enrolled in the High-Risk Breast Program at the UVM Cancer Center. We used Affymetrix miRNA v4 microarrays to interrogate miRNAs (miRBase v20) in the serum of cancer-free women at high-risk for breast cancer. The 24 cases developed breast cancer at least 6 months (average of 3.2 years) and the 24 controls remain cancer-free.
Project description:Background & Aims: Early detection biomarkers for pancreatic ductal adenocarcinoma (PDAC) are needed since the clinically validated biomarker, CA19-9, has limited sensitivity and specificity for early-stage disease. Circulating miRNAs in plasma associated with cancer relevant pathways were developed as early detection biomarkers. Methods: Whole transcriptome assay interrogated 2,083 miRNAs in 15 µl of plasma from multicenter diagnostic cohorts (N=203: controls, n=82; diagnosed PDAC cases: n=121) and a pre-diagnostic PLCO cohort (N=96; controls, n=48; pre-diagnosed cases, n=48). A three-miRNA biomarker signature was developed for early detection of PDAC. Results: The three-miRNA signature detected PDAC from healthy controls independently (AUC = 0.974) and in combination with CA19-9 (AUC = 0.995). It also discriminated from pancreatitis (AUC = 0.931), improving performance of CA19-9 alone (AUC = 0.749) in combination (AUC = 0.954). Blinded validation in pre-diagnostic PLCO cohort revealed lead-time trajectory increase in AUC to 0.702 tat twelve-months before PDAC diagnosis. Conclusions: Plasma miRNAs associated with oncogenic pathways may serve as PDAC early detection biomarkers, with model performance progressively increasing approximately twelve months before diagnosis.
Project description:Up to 50% of ovulations go undetected in modern dairy herds due to attenuated oestrus behavior and a lack of high-accuracy methods for detection of fertile oestrus. This significantly reduces overall herd productivity and constitutes a high economic burden to the dairy industry. MicroRNAs (miRNAs) are ubiquitous regulators of gene expression during both health and disease and they have been shown to regulate different reproductive processes. Extracellular miRNAs are stable and can provide useful biomarkers of tissue function; changes in circulating miRNA profiles have been reported during menstrual cycles. This study sought to establish the potential of circulating miRNAs as biomarkers of oestrus in cattle using Illumina small-RNA sequencing.
Project description:Biomarker studies for early stage or preclinical hepatocellular carcinomas (HCC) are hindered by the difficulties of obtaining samples from asymptomatic individuals. We established animal models using irradiated mice to investigate circulating miRNA as non-invasive markers for detection of early stage HCC. We hypothesized that certain miRNAs that play pivotal roles in molecular pathways are conserved across species and identification of these miRNAs will facilitate studying human markers in mice. To test the hypothesis, we performed weighted gene co-expression analysis by integrating circulating miRNA and tumor gene expression profiles from individual mice and discovered hub miRNAs in highly correlated expression modules. We validated the hub miRNAs using F2 hybrid mice derived from radiogenic HCC susceptible and resistant founders and identified 38 circulating miRNA markers associated with radiation-induced HCC. Through literacy search, we selected 10 human HCC-associated circulating miRNAs that had been validated in multiple independent patient cohorts. Nine of the 10 human markers overlapped with the mouse hub miRNAs, indicating the feasibility of using mouse model to study human circulating HCC markers. Using serially collected plasma samples from irradiated mice, we studied the kinetics of circulating miRNAs. We found that the mouse plasma levels of 4 human circulating markers, miR-122-5p, miR-100-5p, miR-34a-5p and miR-365-3p increased linearly as the time approaching towards HCC detection, indicating the correlations of the 4 miRNAs with oncogenic progression. Estimation of change points in the kinetics of the 4 circulating miRNAs suggested the changes started months before HCC detection, ranging from 17.5 to 6.8 months. Our data demonstrated that the 4 circulating miRNAs were sensitive biomarkers potentially valuable for the screening of early stage HCC.
Project description:circulating microRNA analysis in Subarachnoid hemorrhages (SAH) patients and Heathy controls circulating microRNA profiling has been shown for biomarker discovery for early disease detection in serum, which is stable and accessible. we describe our progress and propose a workflow to investigate and directly compare the circulating microRNA profiles of SAH patients and healthy individuals, in order to characterize potential biomarkers for SAH. Then we verified the top microRNA by quantitative PCR. Informatics analysis of KEGG provided important mechanistic insight to their potential involved pathways. Finally we demonstrated a possible workflow and initial results which indicated that circulating miRNAs can be potential biomarkers of SAH.