Toward the blood-borne miRNome of human diseases

Keller, Andreas; Leidinger, Petra; Bauer, Andrea S.; ElSharawy, Abdou; Haas, Jan; Backes, Christina; Wendschlag, Anke; Giese, Nathalia A.; Tjaden, Christine; Ott, Katja; Werner, J. A.; Hackert, Thilo; Ruprecht, Klemens; Huwer, Hanno; Huebers, Junko; Jacobs, Gunnar; Rosenstiel, Philip; Dommisch, Henrik; Schäefer, Arne S.; Müller–Quernheim, Joachim; Wullich, Bernd; Keck, Bastian; Graf, Norbert; Reichrath, Joerg; Vogel, Britta; Nebel, Almut; Jäger, Sven; Staehler, Peer; Amarantos, Ioannis; Boisguérin, Valesca; Staehler, Cord; Beier, Markus; Scheffler, Matthias; Büchler, Markus W.; Wischhusen, Joerg; Haeusler, Sebastian; Dietl, Johannes; Hofmann, Sylvia; Lenhof, Hans Peter; Schreiber, Stefan; Katus, Hugo A.; Rottbauer, Wolfgang; Meder, Benjamin; Hoheisel, Jöerg; Franke, André; Meese, Eckart

doi:10.1038/nmeth.1682

Cited by 326 publications

(318 citation statements)

References 18 publications

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“…A prior power analysis has demonstrated that these cohort sizes at an alpha error probability of 0.05 and a statistical power of 0.95 require an effect size of below 1.2. In previous studies, we usually discovered miRNAs with respective power and these miRNAs were frequently successfully validated by real-time PCR (14,15).…”

Section: Samplesmentioning

confidence: 99%

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Roth

Keller

Hoheisel

et al. 2015

European Journal of Cancer

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Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3months and was compared to 20 LTS patients with a median OS of 55months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short-and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients. Here we characterized microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analyzed by next generation sequencing.The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS.Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short-and long-term survivors with maximal AUC above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time PCR in a validation cohort consisting of 20 STS and LTS patients.In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients.

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Section: Samplesmentioning

confidence: 99%

Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients

Roth

Keller

Hoheisel

et al. 2015

European Journal of Cancer

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“…Extracellular miRNA functions are varied, and include relaying signals between cells and modulating angiogenesis, neurogenesis, cell proliferation and apoptosis, among others [10]. Changes in composition and concentration of miRNA in the extracellular compartment are in many cases related to pathological processes ongoing in the body, which may allow them to be used in some cases as biological markers of disease activity [11].…”

Section: Characteristics Of Extracellular Mirnamentioning

confidence: 99%

Plasmatic microRNA as Potential Biomarkers of Multiple Sclerosis: Literature Review

2016

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“…Los miRNA pueden encontrarse en el suero humano y pueden ser biomarcadores debido a su alta homogeneidad y estabilidad 15,16 . Inicialmente se identificó que los mecanismos de transporte y liberación de estas moléculas se dan mediante la formación y liberación de exoxomas que se producen por una vía dependiente de ceramidas 17 .…”

Section: Micrornasunclassified