Circulating miRNAs are correlated with tumor progression in prostate cancer

Authors

  • Jan C. Brase,

    Corresponding author
    1. Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany
    • Division of Molecular Genome Analysis, German Cancer Research Center—DKFZ Heidelberg, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
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    • Tel.: +49-6221-42-4647, Fax: +49-6221-42-3454

  • Marc Johannes,

    1. Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany
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  • Thorsten Schlomm,

    1. Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • Maria Fälth,

    1. Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany
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  • Alexander Haese,

    1. Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • Thomas Steuber,

    1. Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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  • Tim Beissbarth,

    1. Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany
    2. Department of Medical Statistics, University Medicine Göttingen, Göttingen, Germany
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  • Ruprecht Kuner,

    1. Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany
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  • Holger Sültmann

    Corresponding author
    1. Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany
    • Division of Molecular Genome Analysis, German Cancer Research Center—DKFZ Heidelberg, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
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    • Tel.: +49-6221-42-4705, Fax: +49-6221-42-3454


  • This article is dedicated to the memory of Professor Annemarie Poustka, who was the founder and head of the Division Molecular Genome Analysis at the DKFZ. She was an inspiring scientist and a wonderful person.

Abstract

Circulating miRNAs have recently been indicated as practicable and promising biomarkers for noninvasive diagnosis in various tumor entities. However, cell-free miRNAs have not been found to correlate with clinicopathological variables in epithelial carcinomas. To learn more about the potential clinical relevance of circulating miRNAs in prostate cancer, we screened 667 miRNAs in serum samples from patients with metastatic (n = 7) and localized prostate cancer (n = 14). Various miRNAs were highly abundant in the sera of patients with metastatic disease, and five upregulated miRNAs (miRNA-375, miRNA-9*, miRNA-141, miRNA-200b and miRNA-516a-3p) were selected for further validation. In the first validation study (n = 45), selected miRNAs were analyzed in a prospectively collected serum set taken from different prostate cancer risk groups. Most of the selected miRNAs were significantly correlated with adverse risk factors when different clinicopathological variables were analyzed. Circulating miRNA-375 and miRNA-141 turned out to be the most pronounced markers for high-risk tumors. Their levels also correlated with high Gleason score or lymph-node positive status in a second independent validation study (n = 71). In addition, the expression levels of miRNA-375 and miRNA-141 were monitored in 72 prostate tissue samples (36 tumor vs. 36 benign). Both miRNAs were highly expressed in all samples and significantly upregulated in the tumors compared to normal tissues. Overall, our observations suggest that miRNA-375 and miRNA-141 expression is enhanced in prostate cancer specimens and their release into the blood is further associated with advanced cancer disease.

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