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

Abstract:

UNLABELLED: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.

journal_name

Clin Chem Lab Med

authors

Kuhlmann JD,Wimberger P,Wilsch K,Fluck M,Suter L,Brunner G

doi

10.1515/cclm-2014-1064

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

605-11

issue

4

eissn

1434-6621

issn

1437-4331

pii

/j/cclm.2015.53.issue-4/cclm-2014-1064/cclm-2014-1

journal_volume

53

pub_type

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