A comprehensive profile of circulating RNAs in human serum

Umu, Sinan Uğur; Langseth, Hilde; Bucher-Johannessen, Cecilie; Fromm, Bastian; Keller, Andreas; Meese, Eckart; Lauritzen, Marianne; Leithaug, Magnus; Lyle, Robert; Rounge, Trine B.

doi:10.1080/15476286.2017.1403003

Cited by 118 publications

(130 citation statements)

References 86 publications

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“…In the discovery cohort, 20 different biofluids were collected in two donors or in a pool of [4][5] donors. In the case/control cohorts, selected biofluids (sputum, CSF, urine and saliva) were collected in [8][9][10][11][12] patients and an equal number of healthy controls. Both small RNA sequencing and mRNA capture sequencing were performed in the discovery cohort.…”

Section: Fig1 Study Flow Chartmentioning

confidence: 99%

“…To date, the characterization of exRNAs in biofluids has mainly focused on small RNAs in blood derived samples [1][2][3][4][7][8][9][10] . MicroRNA (miRNA) is the most studied small RNA biotype in biofluids, but other small RNAs, such as piwi-interacting RNAs (piRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), ribosomal RNAs (rRNAs), transfer RNA fragments (tRNAs) and Y-RNAs have also been identified 5,6,8,[10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

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Charting extracellular transcriptomes in The Human Biofluid RNA Atlas

Hulstaert

Morlion

Cobos

et al. 2019

Preprint

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Extracellular RNAs present in biofluids have emerged as potential biomarkers for disease.Where most studies focus on plasma or serum, other biofluids may contain more informative RNA molecules, depending on the type of disease. Here, we present an unprecedented atlas of messenger, circular and small RNA transcriptomes of a comprehensive collection of 20 different human biofluids. By means of synthetic spike-in controls, we compared RNA content across biofluids, revealing a more than 10 000-fold difference in RNA concentration. The circular RNA fraction is increased in nearly all biofluids compared to tissues. Each biofluid transcriptome is enriched for RNA molecules derived from specific tissues and cell types. In addition, a subset of biofluids, including stool, sweat, saliva and sputum, contains high levels of bacterial RNAs. Our atlas enables a more informed selection of the most relevant biofluid to monitor particular diseases. To verify the biomarker potential in these biofluids, four validation cohorts representing a broad spectrum of diseases were profiled, revealing numerous differential RNAs between case and control subjects. Taken together, our results reveal novel insights in the RNA content of human biofluids and may serve as a valuable resource for future biomarker studies.

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Section: Fig1 Study Flow Chartmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Charting extracellular transcriptomes in The Human Biofluid RNA Atlas

Hulstaert

Morlion

Cobos

et al. 2019

Preprint

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“…Increased level of circulating exosomal PD-L1 is a predictive marker for patient clinical response, e.g., indicating poor prognosis in melanoma patients . Moreover, as it was mentioned, exosomes and other vesicles contain detective levels of different classes of RNA molecules including, protein-coding RNAs (mRNA) and noncoding RNAs (e.g., miRNA) (Umu et al, 2018). Recent studies demonstrated that miRNAs directly or indirectly regulate the expression of different immune checkpoints on T-cells and on Tumor cells or APCs .…”

Section: Liquid Biopsies Biomarkersmentioning

confidence: 99%

Immuno-Oncology Biomarkers for Personalized Immunotherapy in Breast Cancer

Vafaizadeh

Barekati

2020

Front. Cell Dev. Biol.

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The immune checkpoint blockade therapy has drastically advanced treatment of different types of cancer over the past few years. Female breast cancer is the second leading cause of death in the overall burden of cancers worldwide that is encouraging healthcare professionals to improve cancer care management. The checkpoint blockade therapies combined with novel agents become the recent focus of various clinical trials in breast cancer. However, identification of the patients who are responsive to these therapeutic strategies remained as a major issue for enhancing the efficacy of these treatments. This highlights the unmet need in discovery and development of novel biomarkers to add predictive values for prosperous personalized medicine. In this review we summarize the advances done in the era of biomarker studies and highlight their link in supporting breast cancer immunotherapy.

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“…In healthy humans, miR--122 isomiRs have been demonstrated to be present in the circulation with a similar profile of types to our data. 24 Krauskopf et al also used RNA sequencing and reported substantially increased circulating isomiRs with DILI in humans. 25 In mice, Chowdhary et al performed Northern blotting to demonstrate miR--122 isomiRs in the circulation following paracetamol toxicity.…”

Section: Uloq (Concentration Cv) 1578mentioning

confidence: 99%

Direct detection of circulating microRNA-122 using dynamic chemical labelling with single molecule detection overcomes stability and isomiR challenges for biomarker qualification

López‐Longarela

Morrison

Tranter

et al. 2019

Preprint

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Circulating microRNAs are biomarkers reported to be stable and translational across species. miR--122 (miR--122--5p) is a hepatocyte--specific microRNA biomarker for drug-induced liver injury (DILI). Our objective was to develop an extraction--free and amplification--free detection method for measuring miR--122 that has translational utility in context of DILI. We developed a single molecule dynamic chemical labelling (DCL) assay based on miR--122 hybridization to an abasic peptide nucleic acid probe that contained a reactive amine instead of a nucleotide at a specific position in the sequence. The single molecule DCL assay specifically measured miR--122 directly from 10 μL of serum or plasma without any extraction steps, with a fit--for--purpose limit of detection of 1.32 pM. In 192 human serum samples, DCL accurately identified patients at risk of DILI (area under ROC curve 0.98 (95%CI 0.96--1), P<0.0001). The miR--122 assay also quantified liver injury in rats and dogs. When DCL beads were added to serum, the miR--122 signal was stabilised (no loss of signal after 14 days at room temperature). By contrast, there was substantial degradation of miR--122 in the absence of beads (≈60% lost in 1 day). RNA sequencing demonstrated the presence of multiple miR--122 isomiRs with DILI that were at low concentration or not present in healthy patient serum. Sample degradation over time produced more isomiRs, particularly rapidly with DILI. PCR was inaccurate when analysing miR--122 isomiRs, whereas the DCL assay demonstrated accurate quantification. In summary, the DCL assay can accurately measure miR--122 directly from serum and plasma to diagnose liver injury in humans and other species, and can overcome important microRNA biomarker analytical and biological challenges.

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A comprehensive profile of circulating RNAs in human serum

Cited by 118 publications

References 86 publications

Charting extracellular transcriptomes in The Human Biofluid RNA Atlas

Charting extracellular transcriptomes in The Human Biofluid RNA Atlas

Immuno-Oncology Biomarkers for Personalized Immunotherapy in Breast Cancer

Direct detection of circulating microRNA-122 using dynamic chemical labelling with single molecule detection overcomes stability and isomiR challenges for biomarker qualification

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