Startseite Increased level of circulating U2 small nuclear RNA fragments indicates metastasis in melanoma patients
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Increased level of circulating U2 small nuclear RNA fragments indicates metastasis in melanoma patients

  • Jan Dominik Kuhlmann EMAIL logo , Pauline Wimberger , Katja Wilsch , Michael Fluck , Ludwig Suter und Georg Brunner
Veröffentlicht/Copyright: 10. Januar 2015
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Abstract

Background: Melanoma is the most aggressive skin cancer and, despite recent advances in therapy, about 20% of the patients die of their disease. Early relapse detection and monitoring of therapy response are crucial for efficient treatment of advanced melanoma. Thus, there is a need for blood-based biomarkers in melanoma management. Serum-derived U2 small nuclear RNA fragments (RNU2-1f) were previously shown to be blood-based biomarkers for gastrointestinal and gynecologic malignancies. Here we examined whether RNU2-1f may also serve as diagnostic biomarker in advanced melanoma.

Methods: Circulating RNU2-1f levels were quantified by comparative reverse transcription PCR in a training cohort of patients with metastatic melanoma (n=33, thereof regionally metastasized to skin and lymph nodes, n=23, and distantly metastasized, n=10) vs. patients with benign naevi (n=16) vs. healthy controls (n=39). Results were validated in an independent patient cohort with distant metastasis (n=16) vs. controls (n=18).

Results: Circulating RNU2-1f levels in the training cohort were significantly increased in serum of regionally and distantly metastatic patients, compared with patients with benign naevi or healthy controls (p<0.0001) and allowed accurate detection of regional (AUC 0.80) as well as distant (AUC 0.84) metastasis. In the validation cohort, increased RNU2-1f levels were confirmed and enabled highly specific detection of distant metastasis (sensitivity 81%, specificity 100%, AUC 0.94).

Conclusions: This is the first report to suggest a blood-based snRNA serving as a diagnostic biomarker for melanoma metastasis. Our data provide a rationale for further defining clinical utility of circulating RNU2-1f in metastasis detection in the management of melanoma patients at risk of relapse and/or with advanced disease.


Corresponding author: Jan Dominik Kuhlmann, Medical Faculty and University Hospital Carl Gustav Carus, Department of Gynecology and Obstetrics, Technische Universität Dresden, Germany, Fetscherstr. 74, 01307 Dresden, Phone: +49-351-458-2434, Fax: +49-351-458-5844, E-mail: ; and German Cancer Consortium (DKTK), Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany

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Received: 2014-8-4
Accepted: 2014-12-1
Published Online: 2015-1-10
Published in Print: 2015-3-1

©2015 by De Gruyter

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