Integration of miRNA expression analysis of purified leukocytes and whole blood reveals blood-borne candidate biomarkers for lung cancer
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ABSTRACT:
SUBMITTER: Hong G
PROVIDER: S-EPMC11340745 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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Project description:The adaptive response to extreme endurance exercise might involve transcriptional and translational regulation by microRNAs (miRNAs). Therefore, the objective of the present study was to perform an integrated analysis of the blood transcriptome and miRNome (using microarrays) in the horse before and after a 160 km endurance competition. A total of 2,453 differentially expressed genes and 167 differentially expressed microRNAs were identified when comparing pre- and post-ride samples. We used a hypergeometric test and its generalization to gain a better understanding of the biological functions regulated by the differentially expressed microRNA. In particular, 44 differentially expressed microRNAs putatively regulated a total of 351 depleted differentially expressed genes involved variously in glucose metabolism, fatty acid oxidation, mitochondrion biogenesis, and immune response pathways. In an independent validation set of animals, graphical Gaussian models confirmed that miR-21-5p, miR-181b-5p and miR-505-5p are candidate regulatory molecules for the adaptation to endurance exercise in the horse. To the best of our knowledge, the present study is the first to provide a comprehensive, integrated overview of the microRNA-mRNA co-regulation networks that may have a key role in controlling post-transcriptomic regulation during endurance exercise.
| S-EPMC4785432 | biostudies-literature
Project description:The adaptive response to extreme endurance exercise might involve transcriptional and translational regulation by microRNAs (miRNAs). Therefore, the aim of this study was to define an integrative analysis of blood transcriptome and miRNome in horses before and after a long endurance ride (160 km) using equine microarrays. A total of 2,453 genes and 162 miRNAs were found to be differentially expressed (DEG) between animals at rest and after the endurance ride. To gain understanding of the biological functions regulated by the differentially expressed miRNA, we used a hypergeometric test analysis. Notably, we detected 42 differentially expressed miRNAs that putatively regulate a total of 350 depleted DEGs, involved in glucose metabolism, fatty acid oxidation, mitochondrion biogenesis, and immune response pathways. Graphical Gaussian models in an independent validation set of animals confirmed that 4 miRNAs could be strong candidate regulatory molecules for endurance exercise adaptation. This study represents, to the best of our knowledge, the first integrated comprehensive overview of the miRNA-mRNA co-regulation networks that may play a central role in controlling post-transcriptomic regulations during endurance exercise in horses.
2016-09-04 | GSE73102 | GEO
Project description:The adaptive response to extreme endurance exercise might involve transcriptional and translational regulation by microRNAs (miRNAs). Therefore, the aim of this study was to define an integrative analysis of blood transcriptome and miRNome in horses before and after a long endurance ride (160 km) using equine microarrays. A total of 2,453 genes and 162 miRNAs were found to be differentially expressed (DEG) between animals at rest and after the endurance ride. To gain understanding of the biological functions regulated by the differentially expressed miRNA, we used a hypergeometric test analysis. Notably, we detected 42 differentially expressed miRNAs that putatively regulate a total of 350 depleted DEGs, involved in glucose metabolism, fatty acid oxidation, mitochondrion biogenesis, and immune response pathways. Graphical Gaussian models in an independent validation set of animals confirmed that 4 miRNAs could be strong candidate regulatory molecules for endurance exercise adaptation. This study represents, to the best of our knowledge, the first integrated comprehensive overview of the miRNA-mRNA co-regulation networks that may play a central role in controlling post-transcriptomic regulations during endurance exercise in horses. Sixty-one Arabian or half-breed Arabian horses (20 females and 41 geldings) aged 10 ± 2 years (±SEM) were recruited on voluntary basis of the owner on three 160 km endurance rides.
2016-09-04 | E-GEOD-73102 | biostudies-arrayexpress
Project description:PurposeGlaucoma, a leading cause of blindness worldwide, often remains undetected until irreversible vision loss has occurred. Treatments focus on lowering intraocular pressure (IOP), the only modifiable and readily measurable risk factor. However, IOP can vary and does not always predict disease progression. MicroRNAs (miRNAs) are promising biomarkers. They are abundant and stable in biological fluids, including plasma and aqueous humor (AqH). We aimed to identify differentially expressed miRNAs in AqH and plasma from glaucoma, exfoliation syndrome (XFS), and control subjects.MethodsPlasma and AqH from two ethnic cohorts were harvested from glaucoma or XFS (often associated with glaucoma, n = 33) and control (n = 31) patients undergoing elective surgery. A custom miRNA array measured 372 miRNAs. Molecular target prediction and pathway analysis were performed with Ingenuity Pathway Analysis (IPA) and DIANA bioinformatical tools.ResultsLevels of miRNAs in plasma, a readily accessible biomarker source, correlated with miRNA levels in AqH. Twenty circulating miRNAs were at least 1.5-fold higher in glaucoma or XFS patients than in controls across two ethnic cohorts: miR-4667-5p (P = 4.1 × 10-5), miR-99b-3p (P = 4.8 × 10-5), miR-637 (P = 5.1 × 10-5), miR-4490 (P = 5.7 × 10-5), miR-1253 (P = 6.0 × 10-5), miR-3190-3p (P = 3.1 × 10-4), miR-3173-3p (P = 0.001), miR-608 (P = 0.001), miR-4725-3p (P = 0.002), miR-4448 (P = 0.002), and miR-323b-5p (P = 0.002), miR-4538 (P = 0.003), miR-3913-3p (P = 0.003), miR-3159 (P = 0.003), miR-4663 (P = 0.003), miR-4767 (P = 0.003), miR-4724-5p (P = 0.003), miR-1306-5p (P = 0.003), miR-181b-3p (P = 0.004), and miR-433-3p (P = 0.004). miR-637, miR-1306-5p, and miR-3159, in combination, allowed discrimination between glaucoma patients and control subjects (AUC = 0.91 ± 0.008, sensitivity 85.0%, specificity 87.5%).ConclusionsThese results identify specific miRNAs as potential biomarkers and provide insight into the molecular processes underlying glaucoma.
| S-EPMC6329203 | biostudies-literature
Project description:Confounding due to cellular heterogeneity represents one of the foremost challenges currently facing Epigenome-Wide Association Studies (EWAS). Statistical methods leveraging the tissue-specificity of DNA methylation for deconvoluting the cellular mixture of heterogeneous biospecimens such as whole blood, offer a promising solution. However, their performance depends entirely on the library of DNA methylation markers being used as the basis for deconvolution. The objective of this study was to train and validate an algorithm for the identification of optimal DNA methylation libraries for the deconvolution of adult human whole blood.
2016-02-12 | GSE77797 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-09-04 | GSE73104 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-09-04 | E-GEOD-73104 | biostudies-arrayexpress
Project description:BackgroundSynovial sarcoma account for approximately 10 % of all soft-tissue tumors and occur most frequently in young adults. A specific translocation in this sarcoma induces fusion of the SYT gene on chromosome 18 to the SSX genes on chromosome X, leading to proliferation of the tumor cells. The need for non-invasive biomarkers indicating recurrence and activity of this disease has sparked research into short non-coding RNA known as microRNA (miRNA).MethodsBlood samples of patients with active synovial sarcoma and of synovial sarcoma patients in complete remission as well as of healthy donors and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma were collected. Whole blood RNA was extracted and samples of patients with active synovial sarcoma and of healthy donors were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm a panel of miRNAs which where differentially expressed in the miRNA array. This miRNA-panel was further evaluated in patients with synovial sarcoma in complete remission and patients with active leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma as well as in an independent cohort of synovial sarcoma patients.ResultsUnsupervised hierarchical clustering of the miRNA arrays separated patients with active synovial sarcoma from healthy controls. A panel of seven miRNAs (miR-99a-5p, miR-146b-5p, miR-148b-3p, miR-195-5p, miR-223-3p, miR-500b-3p and miR-505-3p) was further validated by qRT-PCR to be significantly upregulated in synovial sarcoma patients. Moreover, most of the analyzed miRNAs were shown to be significantly upregulated in synovial sarcoma patients compared to leiomyosarcoma, MPNST, Ewing sarcoma and liposarcoma patients. Validation of the miRNA panel in an independent cohort of synovial sarcoma patients confirmed higher expression levels compared to healthy controls and patients in complete remission.ConclusionOur results have identified a specific whole blood miRNA signature that may serve as an independent biomarker for the diagnosis of local recurrence or distant metastasis of synovial sarcoma. It even distinguishes synovial sarcoma from other sarcoma subtypes, thus potentially serving as a specific biomarker for synovial sarcoma.
| S-EPMC4528907 | biostudies-literature
Project description:Accumulated evidence indicates that various types of miRNA are aberrantly expressed in lung cancer and secreted into the bloodstream. For this study, we constructed a serum diagnostic classifier based on detailed bioinformatics analysis of miRNA profiles from a training cohort of 143 lung adenocarcinoma patients and 49 healthy subjects, resulting in a 20 miRNA-based classifier. Validation performed with an independent cohort of samples from lung adenocarcinoma patients (n = 110), healthy subjects (n = 52), and benign pulmonary disease patients (n = 47) showed a sensitivity of 89.1% and specificity of 94.9%, with an area under the curve value of 0.958. Notably, 90.8% of Stage I lung adenocarcinoma cases were correctly diagnosed. Interestingly, this classifier also detected squamous and large cell lung carcinoma cases at relatively high rates (70.4% and 70.0%, respectively), which appears to be consistent with organ site-dependent miRNA expression in cancer tissues. In contrast, we observed significantly lower rates (0-35%) using samples from 96 cases of cancer in other major organs, with breast cancer the lowest. These findings warrant a future study to realize its clinical application as a part of diagnostic procedures for lung cancers, for which early detection and surgical removal is presently the only hope for eventual cure.
| S-EPMC4979017 | biostudies-literature
Project description:The adaptive response to extreme endurance exercise might involve transcriptional and translational regulation by microRNAs (miRNAs). Therefore, the aim of this study was to define an integrative analysis of blood transcriptome and miRNome in horses before and after a long endurance ride (160 km) using equine microarrays. A total of 2,453 genes and 162 miRNAs were found to be differentially expressed (DEG) between animals at rest and after the endurance ride. To gain understanding of the biological functions regulated by the differentially expressed miRNA, we used a hypergeometric test analysis. Notably, we detected 42 differentially expressed miRNAs that putatively regulate a total of 350 depleted DEGs, involved in glucose metabolism, fatty acid oxidation, mitochondrion biogenesis, and immune response pathways. Graphical Gaussian models in an independent validation set of animals confirmed that 4 miRNAs could be strong candidate regulatory molecules for endurance exercise adaptation. This study represents, to the best of our knowledge, the first integrated comprehensive overview of the miRNA-mRNA co-regulation networks that may play a central role in controlling post-transcriptomic regulations during endurance exercise in horses.
2016-09-04 | GSE72973 | GEO